The complex asymmetrical design of the human knee is ancient in origin. The distinctive characteristics of this design were well established more than 300 million years ago. The knees of most classes of tetrapods exhibit similar morphological characteristics, including a bicondylar cam-shaped distal part of the femur, intra-articular ligaments, menisci, and asymmetrical collateral ligaments. The functional characteristics are also similar, with the dynamic point of femorotibial contact moving posteriorly on the tibia in flexion, approximating a four-bar linkage system. The common design and function among knees of tetrapods imply a profound underlying similarity of kinematic principles. Despite the over-all similarity of the design of knees in tetrapods, no ideal animal model exists for the human knee. The human is the only known species that is both plantigrade and biped. By taking into account the retained complex asymmetry of motion of the human knee, such as the differentially greater femoral rollback of the lateral compartment as compared with the medial compartment, external bracing systems and designs for total knee replacement might be improved.