Etiologic factors in culture-negative endocarditis--better referred to as "apparent" culture-negative endocarditis--include (1) previous antibiotic therapy, (2) fastidious, slow-growing bacteria, (3) nonbacterial organisms, (4) right-sided endocarditis, and (5) noninfective endocarditis. Patients with apparent culture-negative endocarditis are more likely to have had prior antimicrobial therapy and to experience major emboli than are patients with endocarditis whose blood cultures are positive within 48 hours. The literature suggests that survival of patients with apparent culture-negative endocarditis is 92% if fever responds to therapy within 1 week but only 50% if they are still febrile after 1 week of therapy. Guidelines for diagnosis and therapy are outlined.