In the epidermis, the thin outermost layer of the skin, melanocytes in close contact with keratinocytes form the so-called epidermal-melanin unit. There, melanocytes synthesize the pigment melanin in lysosome-related organelles called melanosomes that are further transferred to keratinocytes in order to color the skin and to provide photo-protection against UV solar radiations. Melanocytes and keratinocytes communicate by direct contacts as well as the release of soluble factors and of Extracellular Vesicles, like exosomes. Such intercellular communication is crucial to regulate the biogenesis of melanosomes, their transfer to keratinocytes, as well as their fate in keratinocytes. All these processes and the involved components are thus key to dictate the pigmentation status of the skin, its capacity to photo-protect, and can be targeted in inherited pigmentary disorders, like albinisms and skin cancers.