A 46-year-old man with HIV infection and active intravenous drug use presented with approximately two weeks of fevers and body aches. On physical examination he was somnolent, had a new systolic murmur, bilateral conjunctival hemorrhages, diffuse petechiae, and left-sided arm weakness. Echocardiography revealed a large mitral valve vegetation and brain imaging demonstrated numerous embolic infarctions. Blood cultures grew Serratia marcescens. Despite aggressive treatment with meropenem the patient died due to intracranial hemorrhage complicated by herniation. Serratia marcescens is an uncommon cause of infective endocarditis. While this disease has historically been associated with intravenous drug use, more recent reports suggest that it is now largely a consequence of opportunistic infections of the chronically ill. Our case highlights several characteristic features of this infection, including isolation of a non-pigmented strain of the organism, an antibiotic susceptibility profile suggestive of AmpC β-lactamase production, and rapid clinical deterioration with multiple embolic complications resulting in death. In this review we discuss the history, epidemiology, and management of endovascular infections due to Serratia spp., emphasizing the continued importance of considering this organism in the differential diagnosis of endocarditis among intravenous drug users and as a potential indication for surgical therapy.