With infective endocarditis afflicting 15,000 patients each year and with a mortality rate that still hovers at almost 40%, the disease remains a very serious health problem. Surprisingly, the incidence has not declined over the last 30 years, and now with more health care interventions, such as pacer/defibrillators, and an increasingly elderly population with degenerative valvular heart disease, the number susceptible to endocarditis is actually increasing. Given the weak evidence for endocarditis prophylaxis, there remains a large population at risk. Much has been learned recently about the pathogenesis of endocarditis, including the role of endothelial damage, platelet adhesion, and microbial adherence to the vegetation or intact valvular tissue. Three-fourths of patients have preexisting structural heart disease. Once infection is manifest, major cardiac complications include congestive heart failure, embolization, mycotic aneurysms, renal dysfunction, and abscess formation. The diagnosis of endocarditis has been enhanced recently by modifications in the Duke criteria to include the use of transesophageal echocardiography and microbial antibody titers. Surgery continues to play an important role, with criteria for emergency, urgent, and early surgery now defined. The major organisms involved in infective endocarditis include streptococci and staphylococcus (representing 75% or so of all cases). Enterococcal infections account for many of the remaining cases, although small series and case reports suggest almost all organisms that infect humans can be implicated at times. A sizeable number of "culture-negative" cases still occur despite all the improvements in diagnostic methodology. Recent guidelines for the diagnosis, treatment, and management of infective endocarditis from the American Heart Association are reviewed and the issues surrounding prophylaxis are summarized. International cooperative databases are now being developed that hold promise for a continual reexamination of the epidemiology of this highly aggressive disease and may help provide sorely needed prospective trial data that will enhance our understanding and treatment.