Leukocyte- and platelet-rich fibrin (L-PRF), a by-product of centrifuged autologous whole blood, contains high concentrations of platelets, leukocytes, and fibrin (the latter spontaneously creating a strong 3-D network (a membrane)). L-PRF membranes possess several characteristics essential in wound healing, including a barrier function, an antibacterial and analgesic activity, and the release of growth factors enhancing tissue regeneration and neo-vasculogenesis. This review investigated the role of L-PRF in treating non-responding chronic wounds such as diabetic foot, venous leg ulcers, pressure ulcers, complex wounds, leprosy ulcers (Hansen's Disease), and other demanding wounds. Chronic wounds affect millions worldwide, negatively impacting their quality of life, productivity, and life expectancy while incurring high treatment costs for themselves and private and public health systems. L-PRF has demonstrated clear adjunctive advantages in treating chronic skin wounds, shortening the time to complete wound closure, and improving patient-reported outcome measures (including reducing pain and minimizing the need for analgesics). Also, in other demanding wounds, L-PRF facilitates healing. To help clinicians, this article also proposes recommendations for the use of L-PRF in the treatment of extra-oral wounds.