The basic etiology of neuropathic diabetic foot wounds involves pressure in conjunction with cycles of repetitive stress, leading to failure of skin and soft tissue. The central tenet of any treatment plan addressing neuropathic diabetic foot wounds is the appropriate debridement of nonviable tissue coupled with adequate pressure relief (off-loading). Although numerous advances have been made in the treatment of diabetic foot wounds, including bioengineered tissues, autologous and exogenous cytokine delivery systems, and potentially effective topical antimicrobial modalities, none will succeed without addressing effective debridement and off-loading. Specific debridement and off-loading techniques are discussed, along with available supporting evidence. This includes the use of the "instant" total contact cast, among other modalities.