Owing to economic conditions, removable dentures remain popular despite the discomfort and reduced chewing efficiency experienced by most denture wearers. However, there is little evidence to confirm that the level of mucosal load exceeds the pressure pain threshold. This discrepancy stimulated us to review the current state of knowledge on the biomechanics of mastication with complete removable dentures. The loading beneath dentures was analyzed in the context of denture foundation characteristics, salivary lubrication, occlusal forces, and the biomechanics of mastication. The analysis revealed that the interpretation of data collected in vivo is hindered due to the simultaneous overlapping effects of many variables. In turn, problems with determining the pressure beneath a denture and analyzing frictional processes constitute principal limitations of in vitro model studies. Predefined conditions of finite element method simulations should include the effects of oblique mastication forces, simultaneous detachment and sliding of the denture on its foundation, and the stabilizing role of balancing contacts. This review establishes that previous investigations may have failed because of their unsubstantiated assumption that, in a well-working balanced occlusion, force is only exerted perpendicular to the occlusal plane, allowing the denture to sit firmly on its foundation. Recent improvements in the simulation of realistic biomechanical denture behavior raise the possibility of assessing the effects of denture design on the pressures and slides beneath the denture.