Advances in surgical technique and better knowledge of the physiologic and immunologic changes in the transplant population, combined with improved diagnostic tools and treatment strategies, have decreased the likelihood of early and, possibly, late mortality caused by a primary infection. Nevertheless, infection continues to be an important cause of death in both the early and late post-transplant periods. Risk of death attributable to infection after prolonged survival, however, is greatest in the setting of chronic rejection. The most significant advances in antimicrobial management have been in the area of prophylaxis. The effectiveness of prophylaxis against P carinii has virtually eliminated that organism as a cause of significant morbidity. Ganciclovir prophylaxis protocols require refinement but have been proved effective against CMV, although that virus continues to be a major pathogen in lung transplant recipients. Ultimately, a careful monitoring protocol and a high index of suspicion for infection requiring investigation and treatment are necessary in the ongoing care of lung transplant recipients. The approach to infections should be guided by the knowledge of the various factors that increase susceptibility to microorganisms and any previous culture and sensitivity results. As transplant physicians try to increase the donor pool through the use of donors who previously might have been rejected and through the potential of xeno-transplantation, vigilance and research must be maintained.