Clotrimazole is a broad-spectrum antimycotic drug mainly used for the treatment of Candida albicans and other fungal infections. A synthetic, azole antimycotic, clotrimazole is widely used as a topical treatment for tinea pedis (athlete's foot), as well as vulvovaginal and oropharyngeal candidiasis. It displays fungistatic antimycotic activity by targeting the biosynthesis of ergosterol, thereby inhibiting fungal growth. As well as its antimycotic activity, clotrimazole has become a drug of interest against several other diseases such as sickle cell disease, malaria and some cancers. It has also been combined with other molecules, such as the metals, to produce clotrimazole complexes that show improved pharmacological efficacy. Moreover, several new, modified-release pharmaceutical formulations are also undergoing development. Clotrimazole is a very well-tolerated product with few side effects, although there is some drug resistance appearing among immunocompromised patients. Here, we review the pharmaceutical chemistry, application and pharmacology of clotrimazole and discuss future prospects for its further development as a chemotherapeutic agent.