The Sertoli Cell-Only Syndrome (SCOS), also documented as Del Castillo syndrome or germ cell aplaysia, is a exceptional histopathological situation of the testes categorized by the complete lack of germ cells within the seminiferous tubules, leaving only Sertoli cells. It also represents an significant cause of non-obstructive azoospermia (NOA) and male infertility. The cause of SCOS is multifactorial, linking genetic disease, environmental influences, and cryptogenic mechanisms. Male sex glands (Testes) from male with hypogonadotropic hypogonadism showed only immature Sertoli cells; cryptorchid testes showed dysgenetic cells and occasional typical cells; and after heal with oestrogens or chemotherapy the testes showed involuting cells and normal cells. This review paper highlights the existing perceptive of SCOS, consist of its pathogenesis, analytical approach, and therapeutic strategy, while emphasizing modern advances in reproductive medication and forthcoming upcoming strategy.