In the past two decades significant progress has been made in uncovering the biological function of selenium. Selenium, an essential trace element, is required for the biogenesis of selenocysteine which is then incorporated into selenoproteins. These selenoproteins have emerged as central regulators of cellular antioxidant capacity and maintenance of redox homeostasis. This review provides a comprehensive examination of the multifaceted functions of selenoproteins with a particular emphasis on their contributions to cellular antioxidant capacity. Additionally, we highlight the promising potential of targeting selenoproteins and the biogenesis of selenocysteine as avenues for therapeutic intervention in cancer. By understanding the intricate relationship between selenium, selenoproteins, and reactive oxygen species (ROS), insights can be gained to develop therapies that exploit the inherent vulnerabilities of cancer cells.