Climate change and the consequential unpredictable environmental stress conditions negatively impact crop productivity. It has thus become a challenge to develop solutions for food security and sustainable agriculture in the backdrop of increasing population pressure and dwindling land and water resources. This further necessitates that focus of international research should be on curtailing yield losses through improved crop breeding practices and genetic manipulation for the development of resistant crop varieties. Plants being sessile, have developed a complex regulatory network of genetic machinery which includes transcription factors, small RNAs, signalling pathways, stress sensors and defense pathways. Needless to say, research efforts have exploited this genetic reservoir for manipulating crop plants for tolerance or resistance against different stresses. In the past few decades, significant achievement has been made for developing transgenic plants for a wide variety of single or multiple stress tolerance associated traits. Several regulatory mechanisms have been identified to fine tune and tailor the tolerance response in target sensitive crops. The advent of metabolic engineering has added new dimensions to manipulate stress tolerance pathways. Novel strategies are needed to develop stable, superior performing lines under challenging field environment without yield penalty and significant success has to be achieved to translate the research outcome from lab-to-land to reach farmer's fields.