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Heavy metal (HM) toxicity has become a global concern in recent years and is imposing a severe threat to the environment and human health. In the case of plants, a higher concentration of HMs, above a threshold, adversely affects cellular metabolism because of the generation of reactive oxygen species (ROS) which target the key biological molecules. Moreover, some of the HMs such as mercury and arsenic, among others, can directly alter the protein/enzyme activities by targeting their –SH group to further impede the cellular metabolism. Particularly, inhibition of photosynthesis has been reported under HM toxicity because HMs trigger the degradation of chlorophyll molecules by enhancing the chlorophyllase activity and by replacing the central Mg ion in the porphyrin ring which affects overall plant growth and yield. Consequently, plants utilize various strategies to mitigate the negative impact of HM toxicity by limiting the uptake of these HMs and their sequestration into the vacuoles with the help of various molecules including proteins such as phytochelatins, metallothionein, compatible solutes, and secondary metabolites. In this comprehensive review, we provided insights towards a wider aspect of HM toxicity, ranging from their negative impact on plant growth to the mechanisms employed by the plants to alleviate the HM toxicity and presented the molecular mechanism of HMs toxicity and sequestration in plants.