A key foundation for research into the link between stress and ill-health has been the reactivity hypothesis; cardiovascular reactivity to psychological stressors, if prolonged or exaggerated, can promote the development of cardiovascular disease. This has been extended, such that by implicating stress in the aetiology of heart disease, it is plausible that psychosocial stress correlates can influence disease risk. Effects of several risk factors and stress buffers on reactivity have been investigated, but such research warrants scrutiny. Considerable literature links heightened reactivity to objective cardiovascular outcomes, but the evidence extending the reactivity hypothesis to other health outcomes and correlates of heart disease is less clear. Here, we explore the external, concurrent, internal, and construct validity of theories arising from the reactivity hypothesis. We aim to highlight theoretical and methodological considerations to guide future research, and clarify the contribution of the reactivity hypothesis to explaining the consequences of stress.