During the last two decades the incidence of systemic fungal infections has been rising steadily. The prognosis of infected patients is often poor and the therapeutic strategies are limited. The prophylaxis of systemic fungal infections thus appears worthwhile. The substances available comprise the azoles fluconazole and itraconazole and the polyenes amphotericin B and nystatin. If candida infections are to be targeted fluconazole can be used. The adequate dose is 400 mg daily. Compliance usually is satisfactory and toxicity-related adverse events are rare. Itraconazole covers a broader spectrum which encompasses all relevant fungi. Capsules and oral solution of itraconazole do not achieve reliably the therapeutic serum level of about 500 ng/ml. An intravenous formulation of itraconazole has recently been approved in the United States, but there is a scarcity of data with regard to its prophylactic use. Concomitant vinca alkaloid medication may result in life-threatening toxicities. High-dose intravenous amphotericin B has been proven effective for prophylaxis. Due its toxicity profile prophylactic amphotericin B should be used only for selected cases and in clinical studies. Nystatin can be used topically whenever topical amphotericin B is not well tolerated. All currently available prophylactic antimycotics bear the risk of either unsatisfactory effectiveness or severe toxicity.