Acremonium species are filamentous, cosmopolitan fungi frequently isolated from plant debris and soil that have emerged as an important cause of morbidity and mortality in immunocompromised patients. We present data from two hematologic malignancy patients with Acremonium fungemia who had refractory disease despite initial treatment with Amphotericin B with clinical response after changing therapy to Voriconazole. Acremonium should be considered in the differential diagnosis of patients with clinical presentation suggestive of fungal infection and special attention should be given to the treatment challenge it represents.