It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of our body form. As our bodies have adapted to run, it seems unusual that up to 79% of modern day runners are injured annually. The etiology of these injuries is clearly multifactorial. However, 1 aspect of running that has significantly changed over the past 50 years is the footwear we use. Modern running shoes have become increasingly cushioned and supportive, and have changed the way we run. In particular, they have altered our footstrike pattern from a predominantly forefoot strike (FFS) landing to a predominantly rearfoot strike (RFS) landing. This change alters the way in which the body is loaded and may be contributing to the high rate of injuries runners experience while engaged in an activity for which they were adapted. In this paper, we will examine the benefits of barefoot running (typically an FFS pattern), and compare the lower extremity mechanics between FFS and RFS. The implications of these mechanical differences, in terms of injury, will be discussed. We will then provide evidence to support our contention that FFS provides an optimal mechanical environment for specific foot and ankle structures, such as the heel pad, the plantar fascia, and the Achilles tendon. The importance of footwear will then be addressed, highlighting its interaction with strike pattern on mechanics. This analysis will underscore why footwear matters when assessing mechanics. Finally, proper preparation and safe transition to an FFS pattern in minimal shoes will be emphasized. Through the discussion of the current literature, we will develop a justification for returning to running in the way for which we were adapted to reduce running-related injuries.