Infective endocarditis (IE) remains a serious and deadly disease. The incidence, which varies by gender and on the presence of predisposing factors, has not decreased, due in part to the aging population with more healthcare exposures and predisposing risk factors such as prosthetic heart valves and intracardiac devices. The most important aspects of treatment in IE hinge upon early diagnosis, microorganism identification with susceptibility testing, and early initiation of appropriate antibiotic therapy. In addition, echocardiographic imaging is critical for both diagnostic and prognostic purposes. Early evaluation for surgery should be considered. Once a therapeutic strategy is begun, careful attention to the clinical course is necessary to ensure appropriate response to therapy and to identify complications early.