When the concept of apoptosis was introduced in the 1970s, 1 it attracted only limited attention. However, less than two decades ago, Horvitz and colleagues2–4 identified its essential genetic components in the roundworm, Caenorhabditis elegans, and apoptosis emerged as a significant research front. The explosion of knowledge that took place is represented by the accumulation of 25 000 studies in the last 5 years alone. It is now clear that apoptosis is an important aspect of normal organ development and cellular regulation and that it plays a role in a wide variety of physiological and pathological conditions. However, there is still much debate and controversy concerning the role of apoptosis in heart failure. To address the issues of its presence in, significance for, and overall contribution to heart failure, we will review the currently available literature and then discuss its implications for future research and treatment strategies in heart failure.