The therapeutic relationship between patient and clinician is a vital component of psychological and physical treatments, and it is an important contributor to the placebo effect. Yet, as compared with the more technical aspects of health care, relatively little attention is paid to the potential of the patient–clinician relationship to maximize patient outcomes. Here, we review the evidence that the therapeutic relationship is an important predictor of health care outcomes, both in psychotherapy and in physical treatments, as well as in their placebo controls. We also discuss recent advances in social neuroscience, including neuroimaging studies that have identified neural correlates of aspects of the patient–clinician interaction, especially in placebo responding. We then elucidate how focusing on the relational component of placebo treatments may contribute to the identification of placebo responders, using psychological and genetic traits as predictors. Finally, we briefly discuss the implications of this research for clinical practice and training, as well as some pertinent ethical issues that arise from our increased knowledge about factors that contribute to successful patient–clinician interactions.