A complete understanding of how the nervous and endocrine systems interplay within an organism is pivotal for the full characterization of the regulation of its physiological processes, as well as the interaction with its surroundings. These topics are now of major interest in the context of the existing threats linked with global change. In this chapter, we review the current knowledge regarding how anemonefishes respond and acclimate to environmental cues at the morphological, physiological, and behavioural levels. We focus on two natural life history events, metamorphosis and protandrous (male-to-female) sex change, both reflecting the extraordinary phenotypic plasticity of Amphiprioninae, and the potential ways in which the stress axis could mediate these transformations. Additionally, we highlight existing research on the consequences of ocean warming and acidification on these valuable teleost fishes. Finally, we synthesize the scarce data available to date in anemonefishes, an emerging biological model, together with knowledge acquired in this field using canonical fish species (e.g., zebrafish, medaka) or species of economic importance (e.g., salmonids, sea bass).