SHBG is a glycoprotein that not only controls serum sex hormone levels but is also strongly correlated with metabolic syndrome, cardiovascular risk, thyroid function, gynecological conditions, and even the process of carcinogenesis. Synthesis of SHBG is controlled by many factors related to obesity, lipogenesis, inflammatory status, and genetic predisposition. By influencing the bioavailability of sex hormones, SHBG regulates their effects not only on the reproductive system, but also cardiomyocytes, vascular epithelium, and more. In this review, we aim to gather and summarize current knowledge on the physiology of SHBG and its association with cardiovascular disease, metabolic syndrome, DM 2, thyroid function, PCOS, hypogonadism, infertility, and its correlations with oral contraception. What is more, genetic alterations are mentioned to highlight SHBG as a potential new diagnostic marker. Furthermore, we assess the clinical usefulness of this parameter in the diagnosis and treatment of patients suffering from the above-specified conditions.