Over the past 20 years, there has been a dramatic increase in the use of physiological tools and experimental approaches for the study of the biological consequences of catch-and-release angling practices for fishes. Beyond simply documenting problems, physiological data are also being used to test and refine different strategies for handling fish such that stress is minimised and survival probability maximised, and in some cases, even for assessing and facilitating recovery post-release. The inherent sensitivity of physiological processes means that nearly every study conducted has found some level of – unavoidable – physiological disturbance arising from recreational capture and subsequent release. An underlying tenet of catch-and-release studies that incorporate physiological tools is that a link exists between physiological status and fitness. In reality, finding such relationships has been elusive, with further extensions of individual-level impacts to fish populations even more dubious. A focus of this article is to describe some of the challenges related to experimental design and interpretation that arise when using physiological tools for the study of the biological consequences of catch-and-release angling. Means of overcoming these challenges and the extrapolation of physiological data from individuals to the population level are discussed. The argument is presented that even if it is difficult to demonstrate strong links to mortality or other fitness measures, let alone population-level impacts of catch-and-release, there remains merit in using physiological tools as objective indicators of fish welfare, which is an increasing concern in recreational fisheries. The overarching objective of this paper is to provide a balanced critique of the use of physiological approaches in catch-and-release science and of their role in providing meaningful information for anglers and managers.