Purpose of ReviewIt has been known for decades that classical conditioning influences pain perception. However, the precise relationship between conditioning and pain remains unclear. In addition, the clinical implications of their relationship are vastly underappreciated. Thus, we aim to (a) examine how conditioning increases or decreases pain sensitivity, (b) assess how conditioning contributes to the development and maintenance of chronic pain, and (c) explore strategies to utilize conditioning to optimize pain treatment.Recent FindingsWe first review studies regarding how classical conditioning alters pain perception with an emphasis on two phenomena where conditioning increases pain sensitivity (i.e., conditioned hyperalgesia) or decreases it (i.e., conditioned hypoalgesia). Specifically, we critically examine empirical studies about conditioned hyperalgesia and conditioned hypoalgesia, explore reasons why conditioning leads to these two seemingly opposite phenomena, and discuss the neural mechanisms behind them. We then highlight how conditioning contributes to the development and maintenance of chronic pain, and present neuroscientific evidence for maladaptive aversive conditioning in chronic pain patients. Moreover, we propose a framework for understanding how to exploit conditioning to optimize pain treatment, including minimizing conditioned hyperalgesia, maximizing conditioned hypoalgesia, and eliminating excessive fear and overgeneralization in chronic pain.SummaryClassical conditioning profoundly modulates the experience of pain and affects the development and maintenance of chronic pain. The relationship between them has far-reaching clinical implications in pain treatment. Further investigations should tackle crucial issues in previous studies, including the complex relationship between conditioning and explicit expectation, and a lack of relevant clinical studies. Resolving these issues, future research would advance our understanding of the nature of pain, help relieve the suffering of patients, and thus contribute to promoting human flourishing.