The alarming increase in the rate of population is one of the foremost concerns of the agriculture sector. In particular, cold stress often limits the productivity of economically important crop species largely due to acute dehydration in plants. To cope with these stress conditions, plants respond in a variety of levels by modulating physiological and molecular changes in their system. Characteristic features of changes occur during cold stress in plants comprising increasing concentration of oxygen radicals, osmotic regulation, and protein kinase and lipid signaling cascade. Each stress response requires a specific combination of these single reactions regulated by transcription factor and cold-responsive genes. By increasing the activity of such regulatory genes, the plant can be enabled to tolerate cold stress. Various scientific reports suggest the combinatorial regulation of these genes along with transcription to engineer efficient cold stress tolerance in plants. This chapter focuses on the basic molecular and genetic approaches used for generating cold stress tolerance in plants.