The reverse total shoulder arthroplasty (rTSA) prosthesis has been demonstrated to be a viable treatment option for a variety of end-stage degenerative conditions of the shoulder. The clinical success of this prosthesis is at least partially due to its unique biomechanical advantages. As taught by Paul Grammont, the medialized center of rotation fixed-fulcrum prosthesis increases the deltoid abductor moment arm lengths and improves deltoid efficiency relative to the native shoulder. All modern reverse shoulder prostheses utilize this medialized center of rotation (CoR) design concept; however, some differences in outcomes and complications have been observed between rTSA prostheses. Such differences in outcomes can at least partially be explained by the impact of glenoid and humeral prosthesis design parameters, surgical technique, implant positioning, patient-specific bone morphology, and usage in humeral and glenoid bone loss situations on reverse shoulder biomechanics. Ultimately, a better understanding of the reverse shoulder biomechanical principles will guide future innovations and further improve clinical outcomes.