Many aspects relating to equipment configuration affect users’ actions in a manual wheelchair, determining the overall mobility performance. Since the equipment components and configuration determine both stability and mobility efficiency, configuring the wheelchair with the most appropriate set-up for individual users’ needs is a difficult task. Several studies have shown the importance of seat/backrest assembly and the relative position of the rear wheels to the user in terms of the kinetics and kinematics of manual propulsion. More recently, new studies have brought to light evidence on the inertial properties of different wheelchair configurations. Further new studies have highlighted the handrim as a key component of wheelchair assembly, since it is the interface through which the user drives the chair. In light of the new evidence on wheelchair mechanics and propulsion kinetics and kinematics, this article presents a review of the most important aspects of wheelchair configuration that affect the users’ actions and mobility.