Due to their broad antimycotic spectrum and the relatively low rate of side effects, the two antifungals caspofungin and voriconazole are considered as attractive therapeutic alternatives to amphotericin B. However, treatment of severe mycotic infections in patients taking co-medication is associated with the risk of severe adverse drug interactions. The risk of such interactions is increased if voriconazole and, much less pronounced caspofungin, are co-administered with drugs which have an inducing or inhibiting effect on the CYP 450 system, primarily on the isoenzymes CYP2C19, CYP2C9 and CYP3A4. This review provides a comprehensive overview on the potential drug interactions of caspofungin and voriconazole in multimorbid patients.