The purpose of this paper is to review selected literature on the relationship of neuropathy and other related factors in foot ulceration and lower extremity amputation. There is strong evidence that sensory loss and mechanical stress are the primary cause of foot ulceration and common factors in the pathway to lower extremity amputation. Foot stress results from extrinsic factors such as footwear and intrinsic factors such as deformity and limited joint mobility. Understanding the interplay of these factors is valuable in identifying persons whose feet are at risk, effectively preventing and treating foot ulcerations and ultimately preventing lower extremity amputation.