The incidence of infective endocarditis (IE) is rising with the increased availability of prosthetic valves and intracardiac devices. In this review, we describe the epidemiologic trends, microbiology, and clinical manifestations of IE. The 2023 Duke-International Society for Cardiovascular Infectious Disease criteria are summarized, as are other laboratory and imaging studies that may aid in IE diagnosis, including novel methods like broad-range bacterial polymerase chain reaction and PET/computed tomography scans. Finally, we discuss optimal IE management, including guideline-directed antibiotic regimens, indications for cardiac surgery, and preliminary data for oral and long-acting parenteral antibiotics.