Prophylaxis of opportunistic infections in patients with human immunodeficiency virus (HIV) infection has been one of the major factors responsible for increasing patient survival. Secondary prophylaxis of most opportunistic infections is warranted, although in most instances the optimal therapy remains to be determined. Primary prophylaxis of opportunistic infections is an attractive concept, as the majority of opportunistic infections are reactivations of latent infections. Primary prophylaxis against Pneumocystis carinii pneumonia is both effective and necessary, but the role for primary prophylaxis against other infections is as yet unclear. Use of prophylactic agents requires careful study for determining the most effective and least toxic forms of prophylaxis that will allow for adequate concurrent antiretroviral therapy but will not induce resistant organisms.