Physical disability is a major quality-of-life concern for patients, with 1.9 million people in the United States known to be relying on a prosthetic limb as of 2018. Thus, the development of improved prosthetics and novel exoskeletal technologies is a prime objective in the field of physical medicine and rehabilitation. Yet, the inability to incorporate dynamic feedback from a user’s intentions (via neural signals) and environmental stimuli is a crucial limitation of current technologies. This deficiency has warranted the application of precise computational approaches to artificial intelligence in recent literature, which we explore in this chapter. Artificial intelligence applications hold promising potential for optimizing prosthetics and exoskeletons, but challenges remain in validating and implementing these methods.