Opportunistic infections are major causes of morbidity and mortality following bone marrow transplantation. Technological advances in stem cell procurement, the introduction of hematologic growth factors to speed engraftment, the development of new immunosuppressive regimens to control graft-versus-host disease (GVHD), the development of technology to perform graft engineering with removal of T lymphocytes in toto or subpopulations of T lymphocytes, the use of molecular techniques to optimize donor and recipient matching, advances in blood banking, and development of international donor registries, are among the various factors that have led to tremendous changes in transplant practices. Because of such changes in transplant practices, along with the advent of new antimicrobial agents, and development of infection control measures affecting pathogen exposure, alterations in the interplay between host and potential pathogens have occurred. Shifts in the incidence and types of opportunistic pathogens are taking place. Several historically important infectious syndromes are today well controlled; others have diminished in importance early after transplant but are more problematic at a later time; new emerging pathogens are being recognized due to selection pressures from antimicrobial usage and new hosts, such as recipients of alternate donor allogeneic transplant procedures, with even more profound and prolonged immune suppression. Such shifts and new syndromes pose continuing new challenges to the transplant clinician.