Environmental stress adversely affects the living organisms. To cope with the deleterious effects of the stresses, organisms have developed tolerance mechanisms which vary from individual to individual. Hence, the stress may be more deleterious for one individual in a particular situation but it may not be deleterious for the others. Environmental stresses trigger enhanced production of reactive oxygen species (ROS), causing an oxidative stress in the organism. Several antioxidants are generated inside the body to maintain optimum level of ROS in the body, and to protect cellular macromolecules from the damages caused by ROS. Excessive ROS production has been correlated with chronic diseases in human beings. Several phytochemicals are produced by plants for protection from the stresses, many of which are equally protective for animals also. The changing climatic conditions not only affect the productivity of crops and animals but the quality of produce is also affected. Advances in the fields of health and nutrition are resulting in the emergence of newer branch of science called nutrigenomics/nutriepigenomics which deals with the application of genomics to assess nutritional requirements of the individual. Growing evidence suggests that DNA methylation, chromatin modifications, and siRNA are involved in epigenetic regulation of genes under environmental stresses. Epigenetic changes have been associated with inactivation/activation of genes influenced by various abiotic and biotic stresses, resulting in the adaptation of an organism to the environment. In human, DNA demethylation of long interspersed nuclear elements has been identified as a useful epimark for early detection of cancer, which may also help in the epigenetic treatment of cancer. Genome editing techniques (like CRISPR-dCas9) may help dissecting the cause and effect of epigenomics variations associated with human diseases. However, further studies would be required to understand the molecular mechanisms of stress tolerance to deal with the stress-associated problems.