Vitiligo is a multifaceted disorder with diverse etiological factors, including genetic predisposition, oxidative stress, autoimmune responses, and neurogenic influences. Recent research has focused on the interferon-gamma (IFN-γ) and CXCL9/10-CXCR3 axis, and the JAK/STAT pathway, highlighting their roles in melanin production inhibition, melanocyte apoptosis, and immune cell recruitment. Cytokines like IL-15, IL-17/23, and TNF-α and pathways such as the Wnt/β-catenin, regulatory T cells (Tregs), heat shock protein 70i (HSP70i), and microRNAs (miRNAs) have also been implicated in vitiligo pathogenesis. This chapter examines small molecules and biologics targeting these pathways, detailing their mechanisms, therapeutic outcomes, and clinical statuses. Apremilast, a phosphodiesterase-4 inhibitor, has shown mixed results in clinical studies. JAK inhibitors, particularly topical ruxolitinib and oral tofacitinib, have demonstrated promising repigmentation effects. WNT signaling agonists and miRNA-based therapies are emerging areas of interest. Enhancing Tregs through direct infusion or microbiota modulation shows potential in regulating immune responses. Afamelanotide, targeting MC1R, promotes repigmentation and reduces oxidative stress. Biologics targeting inflammatory mediators like TNF-α, IL-17/23, and IFN-γ-CXCL9/10-CXCR3 axis offer new therapeutic avenues. However, adverse effects, such as infection risk and cardiovascular concerns, necessitate thorough patient evaluation and monitoring. As research progresses, personalized and targeted therapies for vitiligo are becoming increasingly viable, offering hope for more effective and safer treatments.