Throughout evolution, living beings have had to face and resist adverse conditions that tested their adaptive capacity. As a result, they have developed processes such as hormesis to ensure their survival and their ability to thrive in challenging environments. Currently, this process is recognized as a key mechanism that complements Darwin and Wallace’s theory of evolution, making it necessary to explore its relationship with other processes linked to natural selection such as adaptation, adaptability, plasticity, variation, and variability, among the main ones. Subsequent research within the framework of Neo-Darwinism and Modern Synthesis better explains hormesis and the understanding of the complexity of biological responses. In this framework, there is a great need to put hormesis in context based on the laws of variation and inheritance and establish a consistent, updated, and expanded definition that allows the integration of hormesis with evolutionary processes. In addition, the biological mechanisms through which hormesis may be related to the evolutionary process are discussed.

Hormesis is an adaptive response empirically characterized by a biphasic dose–response pattern, in which low or moderate levels of stress induce stimulatory responses whereas higher levels result in inhibitory or toxic effects. Although the biphasic dose–response pattern provides an empirical basis for identifying hormesis, it does not necessarily establish the adaptive significance of the observed response. Individual physiological, biochemical, or molecular variables may exhibit transient or ontogenetically dependent responses; therefore, fitness-related outcomes may provide an integrative criterion for evaluating the biological consequences and adaptive significance of hormesis. Relatively few studies have simultaneously evaluated, under the same stress factor applied across a defined dose or intensity gradient, both the hormetic performance of plants and the xenohormetic potential of bioactive compounds induced by this stress. Furthermore, this approach is insufficient to explain the complexity of the hormetic phenomenon. Therefore, there is a need to more precisely define how hormesis should be evaluated. This may be achieved by incorporating fitness-related variables, such as survival, growth, and reproductive capacity, together with response variables associated with the physiological, biochemical, and molecular mechanisms involved in stress adaptation, thus providing a framework which may be conceptually extended to xenohormesis. Direct evidence linking stress-induced metabolites to improved consumer fitness remains limited, precluding their interpretation in terms of xenohormetic potential.