The increasing incidence of both mucosal and invasive fungal infections has led to the development of several new systemic antifungal agents. Potent and broad spectrum, third generation triazoles, echinocandins and pneumocandins, fungicidal inhibitors of 1,3-beta glucan synthase, and a liposomal formulation of nystatin have recently entered early clinical trials. Other promising agents with novel targets currently under investigation include the pradimicin family of antibiotics, nikkomycin Z, and perhaps, antimicrobial peptides. Immunomodulation by recombinant cytokines has been extensively studied in the laboratory, and effective antifungal vaccines are on the horizon. In conjuction with currently available agents, including the lipid formulations of amphotericin B, this expanded antifungal armamentarium holds promise to meet the evolving challenges of both invasive and mucosal fungal infections.