ABSTRACT Background Implementation of interprofessional clinical guidelines for the prevention of neuropathic diabetic foot ulceration has demonstrated positive effects regarding ulceration and amputation rates. Current foot care recommendations are primarily based on research regarding the prevention of ulcer recurrence and focused on reducing the magnitude of plantar stress (pressure overload). Yet, foot ulceration remains to be a prevalent and debilitating consequence of Diabetes Mellitus. There is limited evidence targeting the prevention of first-time ulceration, and there is a need to consider additional factors of plantar stress to supplement current guidelines. Objectives The first purpose of this article is to discuss the biomechanical theory underpinning diabetic foot ulcerations and illustrate how plantar tissue underloading may precede overloading and breakdown. The second purpose of this commentary is to discuss how advances in biomechanical foot modeling can inform clinical practice in the prevention of first-time ulceration. Discussion Research demonstrates that progressive weight-bearing activity programs to address the frequency of plantar stress and avoid underloading do not increase ulceration risk. Multi-segment foot modeling studies indicate that dynamic foot function of the midfoot and forefoot is compromised in people with diabetes. Emerging research demonstrates that implementation of foot-specific exercises may positively influence dynamic foot function and improve plantar stress in people with diabetes. Conclusion Continued work is needed to determine how to best design and integrate activity recommendations and foot-specific exercise programs into the current interprofessional paradigm for the prevention of first-time ulceration in people with Diabetes Mellitus.