Blood and marrow transplantation, a curative treatment for a variety of serious diseases, induces a period of sustained immunosuppression predisposing recipients to opportunistic infections. Both for the protection of the individual transplant recipient and as a matter of public health policy, the US Centers for Disease Control and Prevention (CDC) has developed guidelines for the use of vaccination in the prevention of infectious disease following transplantation. This review examines the primary clinical research supporting vaccination policies in this target population. Widely accepted recommendations for transplant recipients based on scientific data are sparse, as few large studies have been conducted in this population. Anecdotal reports, expert advice, summaries, and limited series involving less than 50 patients using surrogate end points form the basis of the scientific literature, with the result being a wide variation in practice. Although based largely on inadequate scientific data, the CDC recommendations offer a pragmatic approach to the prevention of opportunistic disease in hematopoietic transplant recipients and serve as a useful starting point for standardization of practice while defining the direction of future studies in transplant recipients and other immunocompromised hosts.