Introduction: Nowadays, squat exercises are commonly used in rehabilitation centers to expand muscle power and strength. In this study, biomechanics and muscle function have been reviewed during squats. The aim of this study is to recognize the gaps and deficiencies of previous studies and provide suggestions to improve the application and safety of squats for rehabilitation and training purposes. Materials and Methods: PubMed and ScienceDirect databases were searched for studies published in English between 2000 and 2020. The Google Scholar search engine was also used for this purpose. Adopting from Medical Subject Headings (MeSH) terms, the search was conducted with keywords Squat, Biomechanics, Muscle function, and Optimization as well as the combination of these terms. The final analysis was performed on more than 32 articles with a direct relationship to the review subject. Results: The squat exercise was widely investigated for several purposes such as improving techniques, preventing injuries, and promoting muscle function . The most common parameters in kinematics, kinetics, and muscle function context were joint range of motion (ROM), joint maximum torque, especially maximum torque of the knee joint, and quadriceps and hamstring muscles function, respectively. Despite numerous studies examining muscle function, there was not enough information about profound muscles involved in the squat exercise. Furthermore, none of the squat methods were optimized in terms of motion pattern. Conclusion: Performing wide-stance back squat (≥ shoulder width) with natural foot positioning, unrestricted movement of the knees, and full depth while the lordotic curve is maintained is an optimal technique to perform this exercise. But it should be noted that the use of musculoskeletal models to optimize motion pattern and make knowledge on the deep muscle function are beneficial to find gold standards and more use of the squat for clinical and rehabilitation purposes.