Mycetoma is a neglected tropical disease that is associated with poor communities and socioeconomically impaired individuals in the tropical and sub-tropical areas. Interestingly, the disease is caused by either bacteria (actinomycetoma) or fungus (eumycetoma). The latter form of the disease, eumycetoma, is the most common type in Africa. Eumycetoma is characterized by a prolonged disease duration and low cure rate. The effective case management of eumycetoma largely depends on the accurate diagnosis and identification of the causative agent to the species level and evaluating its susceptibility to the available drugs. This review summarizes the currently available and used antifungal agents for the treatment of eumycetoma and discusses optimizing the newly developed antifungals as a potential second line for eumycetoma treatment.