Sacral and trochanteric pressure sores in patients with plegias, and foot ulceration in patients with diabetic neuropathy, are similar because these wounds occur in tissues that do not have normal innervation. While it is recognized that insensitive tissue increases the likelihood of ulceration and recurrence of ulceration, this review attempts to answer the question, Is wound healing impaired in denervated tissue? A review of the scientific literature of the past 35 years demonstrates that all phases of wound healing are impaired in denervated tissue, and these mechanisms are different from those related to one of the underlying diseases, diabetes. Understanding the value of innervation, a goal of wound healing should be to seek strategies that provide reinnervation to these at-risk tissues.