Climate change and the consequential unpredictable environmental stress conditions negatively impact cropproductivity. It has thus become a challenge to develop solutions for food security and sustainable agriculturein the backdrop of increasing population pressure and dwindling land and water resources. This furthernecessitates that focus of international research should be on curtailing yield losses through improved cropbreeding practices and genetic manipulation for the development of resistant crop varieties. Plants beingsessile, have developed a complex regulatory network of genetic machinery which includes transcriptionfactors, small RNAs, signalling pathways, stress sensors and defense pathways. Needless to say, researchefforts have exploited this genetic reservoir for manipulating crop plants for tolerance or resistance againstdifferent stresses. In the past few decades, significant achievement has been made for developing transgenicplants for a wide variety of single or multiple stress tolerance associated traits. Several regulatory mechanismshave been identified to fine tune and tailor the tolerance response in target sensitive crops. The advent ofmetabolic engineering has added new dimensions to manipulate stress tolerance pathways. Novel strategies areneeded to develop stable, superior performing lines under challenging field environment without yield penaltyand significant success has to be achieved to translate the research outcome from lab-to-land to reach farmer’sfields.