Vitiligo is an acquired pigmentary disorder characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. The cause of the destruction of epidermal melanocytes is complex and not yet fully understood. However, there are several hypotheses related to biochemical, neural and genetic aspects as well as oxidative stress and autoimmune mechanisms proposed to understand this disorder. Oxidative stress has a role in vitiligo onset, while autoimmunity contributes to disease progression. In this review, we discuss the mechanisms that link triggering factors with the disease progression. Oxidative stress causes disruption in redox potentials that extend to the Endoplasmic Reticulum (ER), causing accumulation of misfolded proteins, which activates the Unfolded Protein Response (UPR).