Melasma is an acquired, symmetrical hypermelanosis of the face. The pathogenesis of melasma is complex and the treatment is often challenging with frequent relapses. Genetic background, exposure to ultraviolet radiation, and female sex hormones are classical influencing factors. To the light of the recent literature, other factors could promote melasma lesions. Moreover, there are increasing evidences showing that melanocytes are not the only cells involved, and that other players probably have a key role in the development and the relapses of melasma. Identifying those associated factors should provide new targets for a more efficient treatment of melasma and a better prevention of the relapses.