The biopsychosocial model has been used to describe the intertwined factors that may act as mechanisms in cardiovascular disease, as well as those found in pain conditions. This model may also prove useful in understanding a diagnosis that overlaps these two areas, angina. This article reviews the literature related to biological, psychological, and social mechanisms of painful ischemic episodes and discusses the interactions of those variables. We propose an integrated model that incorporates the biopsychosocial mechanisms that may be responsible for the variability in pain reporting with ischemic episodes. We show how sex differences manifested in various biopsychosocial factors may interact to influence the presence of painful versus silent myocardial ischemia. We present a plan for future research to elucidate this interaction.