Infective endocarditis (IE) in elderly patients presents a unique diagnostic and therapeutic challenge. Atypical presentations frequently lead to delayed diagnosis and poor outcome. IE in elderly persons is somewhat more common among men. Underlying degenerative valvular disease, mitral valve prolapse, and the presence of a prosthetic valve are important risk factors predisposing elderly persons to IE. Streptococci and staphylococci are the predominant organisms, which are recovered from approximately 80% of elderly patients with IE. In older patients, IE occurs somewhat more frequently on the mitral valve than it does on the aortic valve. The presence of calcific valvular lesions and the prosthetic valves often confound the echocardiographic findings in elderly patients. A high index of suspicion and an aggressive diagnostic approach are required to ensure timely diagnosis and appropriate therapy.