Immune deficits account for the high frequency of life threatening bacterial, viral, and fungal opportunistic infections seen in allogeneic HSCT recipients. Despite advances in infectious disease management, the integrity of host defenses remains the mainstay of defense. The intensity of the preparative regimen, degree of HLA matching, source of stem cells (marrow, blood, or cord), extent of T-cell depletion, and immunosuppressive therapy are some of the factors that impact the kinetics, characteristics, and quality of immune reconstitution. Graft-versus-host disease and its prophylaxis or treatment produce a host environment that is particularly vulnerable to infections. Mucosal disruption and prolonged severe neutropenia usually confine their impact to the early course of transplant. After initial engraftment, HSCT recipients remain at great risk for opportunistic infections and this is related to prolonged and severe T-lymphocyte dysfunction of a complex multifactorial nature. B cell dysfunction is less problematic clinically, but includes deficiencies of immunoglobulin subclasses and impaired ability to mount a vaccine response. Advances in understanding of these immune deficits have resulted in successful strategies including revaccination, growth factors, thymic protection, and adoptive cellular therapy with antigen-specific cells.