Alcohol abuse is a major risk factor for the development of many infectious diseases, particularly pulmonary infections. Bacterial pneumonia and other lung infections in alcohol-abusing patients are usually severe and associated with a high morbidity and mortality. Normal host defense mechanisms in the respiratory tract consist of both innate and acquired immunity which operate effectively in preventing the invasion of infectious pathogens. Numerous in vivo and in vitro studies have shown that alcohol is an immunosuppressive agent that compromises the function of various components of the immune defense system. In recent years, human immunodeficiency virus infection has become epidemic, especially in individuals who abuse alcohol and other substances. Treatment of pulmonary infections in these immunocompromised hosts has continued to be a major challenge in our health care system. Immunotherapy to improve or enhance pulmonary host defense function in conjunction with aggressive antimicrobial regimens may provide a new approach in the management of infections in these patients.