Infective endocarditis is best characterized as a disease in evolution. The list of patients at risk, which formerly included almost exclusively patients with rheumatic heart disease, is being continuously modified and expanded. Nowadays, patients with prosthetic heart valves, users of illicit intravenous drugs, and patients with mitral valve prolapse rather than patients with rheumatic heart disease account for the majority of cases of infective endocarditis. Moreover, due to the widespread use of indwelling atrial catheters for parenteral nutrition as well as for intensive cytotoxic therapy, catheter-related right-sided endocarditis is emerging among nosocomial infections. With the advent of successful antimicrobial therapy, complications rather than endocardial infection pose the major therapeutic problems. In addition to progressive heart failure, myocardial abscesses, fungal endocarditis, relapsing infection, and major systemic emboli in the presence of large protuberant vegetations constitute indications for replacement of the valve. Despite progresses in diagnosis and therapy, infective endocarditis will most likely continue to challenge physicians even in the next future.