The epidemiology of IE has evolved over the past 50 years. Mitral valve prolapse and degenerative valvular disease have replaced rheumatic heart disease as the most common predisposing conditions. The average age of patients with IE has increased, and nosocomially acquired cases are becoming more common. Although viridans streptococci are currently responsible for a smaller proportion of cases than previously, this group of bacteria remains the most common cause of prosthetic value and native valve endocarditis. Staphylococci are the most important cause in some community hospitals, in nosocomial IE, and in IVDUs. IE is a multisystem disease, and patients may present with diverse clinical features. In the absence of direct histopathologic and microbiologic examination of valvular vegetations, the diagnosis of IE depends on the detection of endocardial abnormalities and the isolation of a pathogen from blood. Blood culture remains the most important laboratory test and yields the causative microorganism in 95% of patients. Echocardiography has become an important tool for detecting endocardial lesions. The clinical features of IE in IVDUs are somewhat different than those in other populations. The microbiology is distinctive, and right-sided involvement with septic pulmonary emboli is the most common clinical scenario in this group.