The most recent estimates show an apparent increase in sudden cardiac death (SCD) in the United States. A major reduction in SCD will depend on developing effective methods to identify and prevent risk factors for SCD. This article reviews the research milestones that have resulted in our current approach to risk stratification and treatment of patients at high risk for SCD. One of the earliest attempts to prevent SCD involved suppression of premature ventricular complexes (PVCs) in high-risk patients, but trials using a variety of antiarrhythmic drugs with the aim of suppressing PVCs and reducing mortality demonstrated negative survival results. In the case of amiodarone, clinical trial data to date suggest that it should not be used for primary prevention of SCD or to prolong survival in patients with congestive heart failure secondary to coronary artery disease. The implantable cardioverter defibrillator (ICD) has been demonstrated in multiple studies to be the most significant therapy for life-threatening ventricular arrhythmias and for primary and secondary prevention of SCD. It is recommended that the majority of patients who receive cardiac resynchronization therapy should have an ICD unit implanted in order to include defibrillator therapy.