Oropharyngeal candidiasis is the most common opportunistic infection seen in patients infected with the human immunodeficiency virus (HIV). As HIV disease progresses and immunosuppression worsens, the incidence and severity of oropharyngeal candidiasis increase. The predominant pathogen in initial and recurrent episodes is Candida albicans, which responds to a variety of topical (nystatin and clotrimazole) and systemic azole antifungal agents (ketoconazole, itraconazole, and fluconazole). Since the introduction of the oral azoles, increasing evidence indicates that C. albicans strains are developing resistance to azoles, particularly fluconazole, and other Candida strains are emerging that are intrinsically less susceptible to azole therapy. The advent of effective antiretroviral therapies for the treatment of HIV disease has led to a scenario in which antifungal strategies are likely to be highly effective. To minimize the risk of resistance, topical therapies should be considered first-line candidates for treatment of initial or recurrent cases of uncomplicated oropharyngeal candidiasis. Systemic azole therapy should be reserved for cases unresponsive to topical therapies or for more severe oropharyngeal candidiasis with esophageal involvement.