Drought stress is one of the most adverse abiotic stresses that hinder plants’ growth and productivity, threatening sustainable crop production. It impairs normal growth, disturbs water relations and reduces water-use efficiency in plants. However, plants have evolved many physiological and biochemical responses at the cellular and organism levels, in order to cope with drought stress. Photosynthesis, which is considered one of the most crucial biological processes for survival of plants, is greatly affected by drought stress. A gradual decrease in CO2 assimilation rates, reduced leaf size, stem extension and root proliferation under drought stress, disturbs plant water relations, reducing water-use efficiency, disrupts photosynthetic pigments and reduces the gas exchange affecting the plants adversely. In such conditions, the chloroplast, organelle responsible for photosynthesis, is found to counteract the ill effects of drought stress by its critical involvement as a sensor of changes occurring in the environment, as the first process that drought stress affects is photosynthesis. Beside photosynthesis, chloroplasts carry out primary metabolic functions such as the biosynthesis of starch, amino acids, lipids, and tetrapyroles, and play a central role in the assimilation of nitrogen and sulfur. Because the chloroplasts are central organelles where the photosynthetic reactions take place, modifications in their physiology and protein pools are expected in response to the drought stress-induced variations in leaf gas exchanges and the accumulation of ROS. Higher expression levels of various transcription factors and other proteins including heat shock-related protein, LEA proteins seem to be regulating the heat tolerance mechanisms. However, several aspects of plastid alterations, following a water deficit environment are still poorly characterized. Since plants adapt to various stress tolerance mechanisms to respond to drought stress, understanding mechanisms of drought stress tolerance in plants will lead toward the development of drought tolerance in crop plants. This review throws light on major droughts stress-induced molecular/physiological mechanisms in response to severe and prolonged drought stress and addresses the molecular response of chloroplasts in common vegetable crops. It further highlights research gaps, identifying unexplored domains and suggesting recommendations for future investigations. © 2021 Informa UK Limited, trading as Taylor & Francis Group.