Due to their stationery nature, plants are exposed to a diverse range of biotic and abiotic stresses, of which heavy metals stress poses as one of the most detrimental abiotic stresses, targeting crucial and vital processes. Heavy metals instigate the over-production of reactive oxygen species (ROS), and in order to mitigate the adverse effects of ROS, plants induce multiple defence mechanisms. Besides the negative implications of overproduction of ROS, these molecules play a multitude of signaling roles in plants, acting as a central player in the complex signaling network of cells. One of the signaling mechanisms it is involved in is the mitogen-activated protein kinase (MAPK) cascade, a signaling pathway used to transduce extracellular stimuli into intracellular responses. Plant MAPKs have been implicated in signaling of stresses, phytohormones and cell cycle cues. However, the influence of various heavy metals on MAPKs activation has not been well documented. In this review, we will attempt to address and summarize several aspects related to various heavy metal-induced ROS signaling, how these signals activate the MAPK cascade and the downstream transcription factors that instigates the plants response to these heavy metals. Moreover, we will highlight a modern research methodology that could characterize the novel genes associated with MAPKs and their roles in heavy metal stress.