The incidence of lower extremity wounds, infections, and amputations continues to increase worldwide. Fortunately, the past decade has seen a surge of activity in research into new modalities in wound healing and, even more recently, prevention. This article discusses the basic physiology of wound healing, with particular attention being paid to current and potential wound healing modalities. These include, among other modalities, discussions of bioengineered skin, hyaluronic acid, subatmospheric pressure therapy, growth factors, and endogenous cytokine stimulation. Emerging concepts targeting prevention through novel methods of patient empowerment, dermal thermometry, and computerized activity monitoring are also discussed.