This work outlines the etiological factors for exercise-related foot blisters and the pertinent prevention strategies related to these causes. Blisters result from shear forces within the epidermis causing cell necrosis. The extent of skin shear is influenced by friction at the skin and other interfaces, various skin characteristics, bony movement, and the shear modulus of the foot ware. The number of shear cycles is another factor in the development of blisters. Key preventative strategies include limiting the number of shear cycles, avoiding moisture and particulate accumulation next to the skin, frequent use of skin lubricants, elimination of pressure points through proper fitting and broken in shoes and callous removal, use of low shear modulus insoles, and induction of skin adaptations through proper training. Other methods requiring further research, but with theoretical support, include the use of taping and low friction patches over high-friction areas, and double-layered or toe socks.