Vitiligo is a common depigmentation disorder classified into nonsegmental vitiligo (NSV) and segmental vitiligo (SV). SV accounts for 5-27.9% of patients with vitiligo. The primary pathogenesis of NSV involves the autoimmune-mediated destruction of melanocytes. Recently, an autoimmune pathogenesis of SV was identified. High levels of melanocyte antigen-specific CD8+ T cells are found in early SV lesional skin infiltrating around melanocytes along the basal layer. Mixed vitiligo suggests an overlap in pathogenesis between SV and NSV. In active SV, serum innate immune cytokines, and CD8+ T cell cytokines are increased. Oxidative stress in SV may activate autoimmune responses. SV pathogenesis is associated with a local cytotoxic response targeting epidermal melanocytes. Theories have been put forward to explain the segmental pattern in SV. The previous basis of the neurogenic theory that SV results from dermatomes is no longer accepted. However, there are still research reports supporting this theory. Evaluating the distribution pattern of SV lesions has provided clues to the mosaicism detection of suspected melanocytic defects at the site of SV lesions, supporting this theory. Evidence points to a cytotoxic response targeting mosaic melanocytes. Understanding SV's autoimmune pathogenesis prompts a reevaluation of immunosuppressive medical treatments for SV. The excellent results of autologous melanocyte transplantation in SV lesions compared with the moderate to limited results in patients with NSV support the mosaicism theory.