Skin wound healing is subject to an intricate regulation, involves many cell populations and molecular mediators, and is one of the key mechanisms that ensures the barrier functions of the skin and the maintenance of body homeostasis. The efficiency of this process is largely determined by the balance of proinflammatory and proregenerative signals, which are mediated by cytokines. The review summarizes the latest data on the role of proinflammatory cytokines, mainly tumor necrosis factor (TNF), interleukin 6 (IL-6), interleukin 1 (IL-1), and interferons (IFNs), in skin wound healing, including those obtained with the use of genome editing techniques and methods of reverse genetics to establish relevant animal models. The roles that proinflammatory cytokines play at various stages of skin regeneration are discussed for both normal state and systemic pathologies, such as diabetes. Promising approaches to treating poorly healing wounds are summarized.