Not so very long ago, it was probably easier to win the lottery than qualify to get an implantable cardioverter-defibrillator (ICD). ICDs were considered extreme measures for the most desperate cases. As such, patients had to have survived not one but two documented episodes of sudden cardiac arrest, be drug refractory, but also be strong enough to be able to undergo a thoracotomy to implant the device. Somehow, some patients qualified and received devices! However, the life-saving potential of ICDs was apparent to many physicians. The ICD world changed when a few committed physicians got together to develop a suite of clinical studies that would explore the implantation of this radical device into arrhythmia-rich populations. The most famous of these studies turned out to be the Multicenter Automatic Defibrillator Implantation Trial (MADIT) and MADIT II. Both MADIT and MADIT II looked at heart attack survivors with impaired left-ventricular function. In the first MADIT trial (published in 1996), patients had to be inducible in an EP study. The study was based on the notion that potentially dangerous ventricular arrhythmias occurred more frequently in post myocardial infarction (MI) patients. A positive EP study was utilized to help further confirm the fact that the patient possessed the necessary arrhythmic substrates to sustain a ventricular arrhythmia. The ICD turned out to reduce all-cause mortality by 54% in the ICD group when compared to the control group. But what if these same patients had not undergone the EP study? MADIT II (published in 2002) dispensed with the EP study and found ICDs still reduced the risk of all-cause mortality by 31% versus the control group (Figure 1). While it is very tempting to view MADIT and MADIT II as two versions of the same study, they were actually set up using two different statistical designs. Thus, it is not really accurate to make head-to-head comparisons of the studies. Both showed a significant mortality benefit for ICDs. Eliminating a positive EP study was also a major step; as we know, EP studies can be difficult procedures for some patients, particularly highly symptomatic, debilitated heart failure patients. MADIT and MADIT II prompted a new indication for ICDs and created a new word in our vocabulary: the primary prevention patient. Primary prevention patients were those who would get an ICD to prevent the first instance of sudden cardiac arrest. This marked a huge departure from our previous appreciation of ICDs. Now an ICD could be prescribed for a prior-MI patient without documented arrhythmias and without an EP study, even if the patient was responded well to drugs. (Figure 2) But while the MADIT studies caused physicians to re-think how to manage MI survivors, other investigators were wondering about patients who had not had a heart attack. Would ICDs confer a mortality benefit on nonischemic patients at high risk for arrhythmic activity? That question was answered by the the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) study, which enrolled patients with nonischemic dilated cardiomyopathy and a LVEF 120 ms with some other criteria applicable to those with a QRS between 120 and 150 ms). The CARE-HF study showed a 37% risk reduction for the primary endpoint (all-cause mortality or first hospitalization for a cardiovascular cause). CRT patients showed a 36% reduction in all-cause mortality alone (secondary endpoint) compared to patients who only received drug therapy. CARE-HF is the first trial to show morbidity and mortality benefits for CRT apart from defibrillation. Although more study is warranted, it appears that CRT works by retarding or even undoing some of the cardiac dysfunction that heart failure causes. Resynchronization therapy is associated with reverse remodeling, reduced symptoms, and now it appears to reduce the occurrence of lethal arrhythmias. (Figure 4) While CARE-HF evaluated only low-voltage CRT devices without defibrillation, it makes sense to believe that adding the rescue benefit of defibrillation in a CRT-D system would be even more beneficial. In fact, many clinicians are already selecting devices for their patients with LV dysfunction based on the notion that CRT restores cardiac function and defibrillation can rescue even if a dangerous arrhythmia breaks through. Clearly, things have changed a lot in the past 15 years in terms of understanding who can benefit from device-based treatments. We can anticipate that our understanding of the electrical management of heart disease will change as well. One of the big unanswered questions for rhythm management devices involves risk stratification. The first MADIT study used a positive EP study as a risk stratifier. That was effective, but EP studies are costly and invasive procedures that can be very hard on debilitated patients. It makes sense for some people to have EP studies, but it would waste resources (and tax patients) to give EP studies to large groups of primary-prevention patients. While LV dysfunction appears to be an important stratifier, it is clear that not all patients with impaired systolic function benefit from devices. LV dysfunction seems to be part of the puzzle, but not the whole picture. For instance, some patients with very severe LV dysfunction (Class IV) are at lower risk of arrhythmic death than patients with more moderate LV dysfunction (Class II). Some clinicians use a long QRS duration as a good marker for ventricular dyssynchrony, but we know that some patients with ventricular dyssynchrony may not exhibit this particular marker. A long QRS duration is not a very elegant marker, but it has a lot of utility, in particular, because it is easy and inexpensive measurement to obtain. The problem arises in that some patients with narrow QRS complexes may also have ventricular dyssynchrony. In short, we have learned and continue to learn more and more about device-based therapy for heart disease, but we still don t have the total picture. We know many of the factors that come into play: a low LVEF score, a prior MI, and long QRS. We have looked at other things too: signal-averaged ECGs, T-wave alternans, positive EP studies, documented history of arrhythmias. Personally, I believe that we are close to finding the formula of the simple, inexpensive, easy way to stratify primary-prevention patients. The very notion of primary prevention would have sounded strange to the doctors, nurses, and technicians who worked on the first generation of ICDs. Today, more and more people will get devices in anticipation of a first event. As we better learn to stratify the primary-prevention population, we can extend the life-saving properties of device-based therapy to those for whom it is literally a matter of life and death.