Cardiac assist devices have emerged as an increasingly important option for circulatory support in patients with advanced congestive heart failure. Infection has been the leading cause of death with use of ventricular assist devices for the past 25 years, and continues to be a major cause of morbidity and mortality in this population. Infections may involve the internal (blood-containing) components, or occur on the external device surfaces. The pump pocket and the percutaneous driveline are particularly vulnerable. In this article we review the pathogenesis, epidemiology, clinical course, and approaches for treatment and prevention of cardiac assist device infections.