The approach to infections in blood and marrow transplant (BMT) recipients involves an understanding of clinical infection syndromes and the natural history of individual infections, taken in the context of patterns of immunosuppression after transplantation and mechanisms underlying immune system reconstitution over time. The conditioning regimen used to prepare the host is a major determinant of host tissue injury and may lead to mucositis or diarrhea, facilitating transmucosal origin of bloodstream infections. Infectious risk also differs between autologous and allogeneic grafts as a consequence of ongoing immunosuppression from graft-versus-host disease and its therapy. Post-transplant complications may mimic infectious processes, and multiple infections may occur in one patient at the same time. Thus, the BMT patient with suspected infection should be evaluated in the context of pretransplant exposure history (infectious disease serologies), conditioning regimen, available culture data from nonsterile mucosal surfaces, previous and recent infections, contemporary transplant complications, and the current degree and duration of neutropenia, cellular immunodeficiency, and hypogammaglobulinemia.