Mucocutaneous candidiasis (MC) is one of the first signs of human immunodeficiency virus (HIV) infection. Over 90% of patients with AIDS will eventually develop oropharyngeal candidiasis (OPC) at some time during their illness, and an additional 10% will develop esophageal candidiasis (EC). Although numerous antifungal agents are available, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole), have replaced older topical antifungals (gentian violet and nystatin) in the management of MC in these patients. The systemic azoles, itraconazole and fluconazole, are generally safe and effective agents in HIV-infected patients with MC. A concern in these patients is the clinical relapse, which appears to be dependent on degree of immunosuppression and is more common following clotrimazole and ketoconazole than with fluconazole or itraconazole. Posaconazole is a new extended-spectrum triazole recently approved for the management of OPC. In vitro, posaconazole possesses potent activity against numerous Candida species, including strains that are resistant to fluconazole. Recent clinical trials demonstrate that posaconazole is as efficacious as fluconazole in producing a successful clinical response in HIV-infected patients with OPC/EC. In addition, posaconazole was safe and more effective in sustaining clinical success after treatment was discontinued. Posaconazole appears to be an effective alternative in the management of MC in this difficult- to-treat population.