Pneumocystis carinii remains an important pathogen in patients who undergo solid-organ and hematopoietic transplantation. Infection results from reactivation of latent infection and via de novo acquisition of infection from environmental sources. The risk of infection depends on the intensity and duration of immunosuppression and underlying immune deficits. The risk is greatest after lung transplants, in individuals with invasive cytomegalovirus disease, during intensive immunosuppression for allograft rejection, and during periods of neutropenia. Prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) prevents many opportunistic infections, including infection with P. carinii, Toxoplasma gondii, and community-acquired respiratory, gastrointestinal, and urinary tract pathogens. Intolerance of TMP-SMZ is common; desensitization is useful less often in transplant patients than in patients with AIDS. Alternative agents provide a narrower spectrum of protection than does TMP-SMZ and less adequate protection against Pneumocystis species. Clinically, the diagnosis of breakthrough Pneumocystis pneumonia often requires invasive procedures. Strategies for the prevention of Pneumocystis infection must be individualized on the basis of a stratification of risk for each patient.