Oral candidal infections are medically treated with antifungal agents. In the fungal cell membrane, steroid ergosterol is the target of the antifungals on the market, but similarity with the human cell membrane may cause host toxicity and unintended reactions. Management of oral candidiasis depends on several factors, some are host-sensitive parameters, systemic diseases and drug exposure, and others are infection-sensitive parameters, duration of the infection and the virulence of the infecting Candida species. Treatment failure might be associated with acquired or native azole resistance in particular in patients with recurrent oral candidiasis. This risk can be reduced if different types of antifungal drugs are used over time or are combined. This chapter focuses on antifungal treatment of the medically compromised patient with oral candidiasis by highlighting the advantages and disadvantages of different antifungals.