Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.