Global climate change has increased average environmental temperatures world-wide, simultaneously intensifying temperature variability and extremes. Growing numbers of studies have documented phenological, behavioral, and morphological responses to climate change in wild populations. As systemic signals, hormones can contribute to orchestrating many of these phenotypic changes. Yet little is known about whether mechanisms like hormonal flexibility (reversible changes in hormone concentrations) facilitate or limit the ability of individuals, populations, and species to cope with a changing climate. In this perspective, we discuss different mechanisms by which hormonal flexibility, primarily in glucocorticoids, could promote versus hinder evolutionary adaptation to changing temperature regimes. We focus on temperature because it is a key gradient influenced by climate change, easy to quantify, and links to hormones are well established We argue that reaction norm studies that connect individual responses to population-level and species-wide patterns will be critical for making progress in this field. We also develop a case study on urban heat islands, where several key questions regarding hormonal flexibility and adaptation to climate change can be addressed. Understanding the mechanisms that allow animals to cope when conditions become more challenging will help in predicting which populations are vulnerable to ongoing climate change.