We present four cases of disseminated zygomycosis that illustrate the characteristic clinical syndromes and natural history of this infection. The zygomycetes affect individuals immunosuppressed by age, drug therapy, or underlying disease. A previous splenectomy or deferoxamine therapy may be an additional factor in the development of disseminated zygomycosis. Clinical syndromes reflect vascular invasion and organ infarction. Diagnosis requires consideration of risk factors followed by biopsy of the affected organ for culture and for demonstration of broad nonseptate hyphae in tissue sections. Despite advancesin the management of many bacterial and fungal infections in the immunosuppressed host, the results of therapy for disseminated zygomycosis remain dismal.