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Agricultural production worldwide has been severely impacted by cold and freezing stresses. Plant capacity to acclimate to environmental conditions in their immediate vicinity largely control their survival, growth, and productivity. Molecular as well as biochemical mechanisms underpinning plant cold acclimation are very complex and interwoven. The cold-impacted plants try to modulate expression of variety genes controlling cell membrane lipid composition, mitogen-activated protein kinase cascade, total soluble proteins, polyamines, glycinebetaine, proline, reactive oxygen species (ROS) scavengers, cryoprotectants, and a large number of cold responsive factors. To this end, this paper dissects the array of transcriptional factors/genes down- or up-regulated, their identification in different plant species, recognition of cold tolerant/resistant transgenic plants, complexity of the mitogen-activated protein kinase cascade, as well as their cross talk under different stresses and molecular mechanisms. Furthermore, it also comprehensively elucidates physio-biochemical interferences in cold acclimation with a particular emphasis on endogenous content as well as exogenously supplied different types of polyamines, ROS, and osmoprotectants. Overall, low temperature stress tolerance or cold acclimation varies greatly among species depending on the stress intensity and duration and type of plant species.