Secretory leukoprotease inhibitor (SLPI) is a low molecular weight serine protease inhibitor found on various mucosal surfaces and has been ascribed an important role in maintaining the protease-anti-protease balance of the airways. Recent scientific evidence has suggested that SLPI may also have a broad spectrum antibiotic activity that includes antiretroviral, bactericidal, and antifungal activity. Given the unpropitious development of drug resistance to infectious micro-organisms in the human population, the need for therapeutic alternatives in the treatment of infectious diseases has become clear. SLPI may prove valuable in the prophylaxis and future treatment of infectious diseases, yet the clinical efficacy of SLPI remains largely to be elucidated.