Melanogenesis is a melanin-forming process responsible for protecting the skin against ultraviolet radiation damage. An excess production of melanin, however, may result in hyperpigmentation (darkening of the skin) to adverse dermatological effects (freckles, solar lentigines, and melasma) and skin cancer. These hyperpigmentary skin disorders may also have a major effect on a person's appearance and could even result in emotional and mental distress, as well as a diminished quality of life. A large number of melanogenesis inhibitors have been discovered, but most of them appeared to have undesirable side effects. Therefore, in order to better understand the mechanisms of hyperpigmentary skin disorders and to establish effective and safe melanogenesis inhibitors, more fundamental research is needed. Apart from tyrosinase blockers, there are also alternative approaches that involve the manipulation of melanogenesis regulatory pathway such as α-melanocyte-stimulating hormone blockers, melanosome transferase inhibitors, and cytokines. This review abridges data on the different melanogenesis inhibitors and depigmentation agents from both natural and synthetic agents from the last few years.