Phytoremediation is a widely studied and applied technology, based on the use of plants and their associated microorganisms to decontaminate polluted sites. In recent years, different strategies have been investigated to improve the phytoremediation efficiency of the selected plants. In this context, some studies have shown that herbicide-safeners, chemicals applied to crops to enhance their tolerance to herbicides, can increase the phytoremediation of soils and water polluted by organic and inorganic contaminants. Safeners, by inducing the xenobiotic detoxification and the antioxidant metabolism in plants, can enhance their removal potential in the cleaning process. In this review, after a short survey of phytoremediation technologies and the biochemical mechanisms activated by plants to tolerate and detoxify heavy metals and herbicides, the use of herbicide-safeners as a tool to increase the phytoremediation performance is reviewed and discussed.