Histoplasmosis, blastomycosis, and coccidioidomycosis are uncommon, but often life-threatening infections in patients who have hematologic malignancies. Disease occurs either as a result of new infection after an environmental exposure or as a result of reactivation of a remote infection. Among patients who have hematologic malignancies, the greatest risk appears to be in those who have cellular immune deficiencies. Severe pulmonary infection and widespread disseminated infection are the most common manifestations of these infections in patients with hematologic malignancies. Early diagnosis is best accomplished by tissue biopsy with histopathologic evaluation for the distinctive tissue forms characteristic of these fungi; confirmation by growth in culture is essential, but slow for histoplasmosis and blastomycosis. Initial treatment in the immunosuppressed host should almost always be with amphotericin B rather than an azole. Azole antifungal agents can be used in those patients who respond quickly to amphotericin B and for those requiring long-term suppressive therapy.