Vitiligo is an acquired depigmentary skin disorder of unknown origin characterized by well-demarcated, white macules of varying size and distribution. Despite relevant new research and progresses, why melanocytes disappear to induce the characteristic achromic lesions of vitiligo is not fully understood. In spite of recent findings implicating genetic, immune and oxidative stress factors, the exact pathogenesis of vitiligo remains obscure. An innovative concept based on a functional cross-talk between the nervous and immune system is emerging. Neuropeptides released from peripheral nerve endings could synergize with new cytokines to adversely affect melanocyte function and viability. Evidence is increasing regarding the role of neuropeptides in the pathogenesis of vitiligo and a new winning approach to vitiligo therapy based on neuropeptides regulation is at the horizon.