Vitiligo is a chronic and complex disease characterized by a variable disease course. The leading hypothesis for its pathophysiology is autoimmune destruction of melanocytes; however, its etiology is multifactorial and not fully understood. Effective treatment remains challenging, often requiring prolonged and combination therapy. The primary goals of treatment are to arrest progression of disease, promote repigmentation, and sustain repigmentation over time and improve quality of life. Currently, ruxolitinib, a topical Janus kinase (JAK) inhibitor, is the only FDA-approved therapy for vitiligo. In addition to topical agents, systemic therapies targeting autoimmune mechanisms are frequently employed, often in combination with topical treatments and phototherapy. Immunosuppressive therapies are used off-label, further highlighting the need for expanded treatment options and more targeted interventions.