OBJECTIVE Infective endocarditis continues to pose major challenges in diagnosis and management despite advances in understanding the epidemiology, microbiology, and pathology of the disease. The purpose of this article is to provide a review of diagnosis, microbiology, and treatment of infective endocarditis, particularly as they are influenced by case definitions. RESULTS Case definitions have a critical effect on the interpretation of trends in infective endocarditis, and recent studies have proposed more specific criteria. Studies have also addressed the appropriate use of echocardiography to assist in the diagnosis and management of infective endocarditis. Staphylococcus aureus has become an increasingly common cause of infective endocarditis, and the microbiology of nosocomial infective endocarditis is changing. Newer techniques are being used to aid in the identification of causal agents in blood culture-negative infective endocarditis. Antimicrobial guidelines for the treatment of infective endocarditis are readily available, including a proposal to avoid premature discharge of patients on outpatient antibiotic therapy. Additional studies have been conducted on combination antibiotic therapy, duration of treatment, dosing of aminoglycosides, alternative agents for gram-positive organisms, aspirin therapy, and surgical interventions. CONCLUSIONS Recent trends in diagnosis, microbiology, and treatment of infective endocarditis are described, and case definitions play a critical role in their interpretation.