The biological concept of “stress”, set out in the works of G. Selye, created an entire scientific direction. It has played and continues to play a major role in the development of biomedical research. Scientific progress leads to filling the term “stress” with new biological content at different levels of study. At the same time, unjustified expansion often leads to a blurring of the concept, clogging with “cryptic” terms that complicate the understanding of the phenomenon. The purpose of the work is to discuss some points that complicate or distort the scientific content of the term “stress”. It seems appropriate to consider stress as a non-specific marker of damage to the organism. It should not be used to describe various non-specific changes caused by routine strain that any living organism constantly experiences. From a genetic point of view, it is proposed to consider the stress phenomenon as a condition that occurs when the body is unable to adapt within the limits of its “reaction norm”, determined by the genotype. Destabilization (especially structural) of the mammalian genome induced by various factors should be considered as an inseparable sign of overstrain of the organism and the formation of stress. Attempts to adapt at the genomic level may lead to changes in the rate and direction of the evolutionary process. It is proposed to differentiate stress taking into account the classification of living organisms and the level of changes being studied.