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Zygomycoses are rare but often lethal mold infections predominantly affecting immunocompromised patients. Over the last years, several tertiary-care cancer centers reported an increase in the incidence of zygomycete infections in allogeneic blood stem cell transplant recipients. These observations are based on a small number of patients and should be considered in the context of a decades-long increase of mold infection rates. Diagnostic obstacles, including the difficult discrimination from the tenfold more frequent aspergilloses, may confound the reported incidences of zygomycete infections. These may be due to changes in frequency, severity and management of graft-versus-host disease promoting filamentous fungal infections, including zygomycoses. Hospitals applying long-term voriconazole prophylaxis in high-risk patients report a significant decrease in aspergillosis rates since the drug became available in 2001. The observation of increased frequencies of zygomycete infections during this period of time is not based on prospective evaluations. Therefore, the causes of these findings remain a matter of debate. Current multicenter trials on antifungal prophylaxis in high-risk patients promise to generate reliable data on the protective effect of antifungals active against molds, and the incidence of zygomycete infections in a controlled setting.