A human hand is a complex biomechanical system, in which bones, ligaments, and musculotendon units dynamically interact to produce seemingly simple motions. A new physiological hand simulator has been developed, in which electromechanical actuators apply load to the tendons of extrinsic hand and wrist muscles to recreate movements in cadaveric specimens in a biofidelic way. This novel simulator simultaneously and independently controls the movements of the wrist (flexion/extension and radio-ulnar deviation) and flexion/extension of the fingers and thumb. Control of these four degrees of freedom (DOF) is made possible by actuating eleven extrinsic muscles of the hand. The coupled dynamics of the wrist, fingers, and thumb, and the over-actuated nature of the human musculoskeletal system make feedback control of hand movements challenging. Two control algorithms were developed and tested. The optimal controller relies on an optimization algorithm to calculate the required tendon tensions using the collective error in all DOFs, and the action-based controller loads the tendons solely based on their actions on the controlled DOFs (e.g., activating all flexors if a flexing moment is required). Both controllers resulted in hand movements with small errors from the reference trajectories (< 3.4 • ); however, the optimal controller achieved this with 16% lower total force. Owing to its simpler structure, the actionbased controller was extended to enable feedback control of grip force. This simulator has been shown to be a highly repeatable tool (< 0.25 N and < 0.2 • variations in force and kinematics, respectively) for in vitro analyses of human hand biomechanics.