<p>Hair follicles play an important role in maintaining the normal functions of the skin. The dynamic and alternating changes of diverse molecular signals determine hair follicle development and regeneration in the skin. Among the signals, Wnts, particularly Wnt10b is characterized to be especially important in regulating hair follicle behavior by specifically activating the canonical Wnt/β-catenin signaling pathway. In this review, we review the role of Wnt10b signaling in hair growth and regeneration. During embryonic development, Wnt10b promotes hair morphogenesis by inducing the formation of dermal papilla. Moreover, Wnt10b/β-catenin signaling not only governs the fate of hair follicle stem cells (HFSCs) but also coordinates HFSCs and melanocyte stem cells to facilitate pigmented hair regeneration. Interestingly, during wound healing, epidermis-derived Wnt10b initiates hair follicle neogenesis by promoting the dedifferentiation of epidermal keratinocytes and inducing the formation of dermal papilla. However, prolonged overexpression of Wnt10b in epidermal keratinocytes is associated with early-stage cell transformation, the occurrence of systemic sclerosis, and even the development of skin neoplasms. Therefore, a deeper understanding of the role of Wnt10b signaling in hair follicle development, regeneration, and skin diseases provides a rational basis for the development of translational medicine.</p>