Melanocytes, the cells responsible for skin pigmentation, are present in other parts of the body, such as the ocular, auditory, nervous, and cardiac systems. Within these systems, their roles serve a different purpose than their classical counterparts in skin as pigment cells. Such roles include cell turnover in retinal pigment epithelium, maintenance of balance and prevention of environmental damage in the auditory neuroepithelium, role-playing as dendritic cells within the leptomeninges, and prevention of oxidative damage in adipose tissue. Vitiligo, commonly known as a skin pigmentation disorder, has also been associated with several systemic disorders, such as Vogt-Koyanagi-Harada disease and Alezzandrini, Kabuki, and MELAS syndromes. Therefore, since these conditions involve compromise of systems in which melanocytes reside, it is not surprising that vitiligo has other systemic associations. The authors present a detailed review of systemic associations of vitiligo and melanocytes' roles in other organ systems with a focus on systemic disease.