Invasive fungal infections are a serious threat to public health, particularly to people with compromised or suppressed immunity. Although the current antifungal therapies have been significantly improved, the outcome is still far from satisfactory, partly due the limited number of classes of clinically available antifungals, the development of resistance to current antifungals, and the challenges of proper and early diagnosis. Recent advances in the development of new antifungals, although still in the investigational stages, offer some new hope of improving the future of antifungal therapy. Here, we review literature regarding the antifungal activities of several FDA-approved drugs, which were originally intended for treating other conditions, as well as newly discovered natural/artificial compounds. We focus on their mechanisms of action, limitations, and potential in treating fungal infections. The diverse mechanisms of action of these compounds summarized here can provide new directions for future endeavors on antifungal drug development.