Clofazimine is primarily used in the treatment of mycobacterial infections, especially as part of multidrug therapy for leprosy (Hansen’s disease). It helps reduce the bacterial load and controls skin-related symptoms such as nodules and discoloration. Due to its anti-inflammatory properties, it is also beneficial in managing erythema nodosum leprosum (ENL), a severe immune complication of leprosy that causes painful skin lesions and systemic inflammation. In recent years, clofazimine has been explored for its activity against other intracellular pathogens, including Mycobacterium tuberculosis. It is considered in the management of multidrug-resistant tuberculosis (MDR-TB) when standard treatments fail, due to its ability to accumulate in macrophages and target bacteria residing within cells. Additionally, clofazimine has shown immunomodulatory effects, influencing cytokine production and macrophage function, which contributes to its therapeutic benefit beyond direct antimicrobial action. Its unique mechanism and long half-life allow for intermittent dosing, improving adherence in resource-limited settings.