Fungal pathogens of the genus Candida form biofilms on catheters and prosthetic devices. These three-dimensional structures composed of yeast and hyphal cells embedded in an extracellular matrix constitute an important pitfall in the management of disseminated Candida infections because of their intrinsic resistance to almost all antifungals in clinical use. Candida biofilms are especially resistant to azoles and amphotericin B but remain sensitive to the newly introduced echinocandins that target cell wall beta-glucan biosynthesis. Antifungal resistance of biofilms results most probably from the conjunction of several mechanisms that act in a time-dependent manner. While drug efflux is likely to contribute to resistance during the early phases of biofilm formation, changes in the sterol composition of membranes might explain the resistance of mature biofilms. The original physiology of mature Candida biofilms is mirrored by specific gene expression patterns that may pinpoint genes important for the acquisition of pleiotropic antifungal resistance.