Heavy metals (HMs) contamination is one of the main abiotic factors affecting crop productivity and also threatens human health via consuming metal-contaminated crops as a food source. Over the past few years, HMs have drawn a lot of attention due to their increased use for commercial purposes and their harmful effects on plants and other life forms, thus threatening human survival. However, several methods have been adopted in recent years to combat the harsh effects of HMs. After phytohormones, the use of mineral nutrients such as selenium (Se) in the prevention of HM stress has been explored by researchers more recently. Selenium is an important micronutrient widely known for its antioxidant properties in plants and animals. Exogenous Se inhibits metal uptake and translocation and improves the antioxidant system, thus imparting resistance to HM toxicity in plants. Moreover, Se also regulates the production of various osmolytes in cells, which helps develop cell osmolarity. Selenium also produces different secondary metabolites in plants’ defense mechanisms against different stresses. The uptake of mineral nutrients is a vital process for plant growth and development, which is also positively correlated with Se under metalloid toxicity. However, to understand the exact mechanism of Se in HM tolerance, different metabolic processes stimulated by Se and their pathways need to be explored. Hence, this review focuses on the role of Se on nutritional status, antioxidant metabolism, interaction with phytohormones and its role in the regulation of various genes involved in Se-induced HM tolerance. Thus, this study will help researchers in the future for the improvement of HM tolerance via Se application in plants.