In this study, we report the results of using fluorine deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to guide the antifungal therapy against chronic disseminated candidiasis in patients with acute leukemia. Three adult patients were enrolled in this study. All patients underwent a series of PET/CT scans during the course of antifungal therapy. Antifungal therapy was modified based on the change of the FDG activity in the known sites of the fungal infection. With the guidance of FDG PET/CT, all 3 patients achieved favorable outcomes with long-term follow-up. FDG PET/CT appeared to be a valuable modality in designing proper antifungal therapy against chronic disseminated candidiasis in patients with acute leukemia.