Acceptance into groups and intimate relationships is necessary for survival and emotional well-being. Thus, even everyday occurrences of social rejection (when one is not wanted or liked) can cause sadness, anxiety and social withdrawal. Studies using functional magnetic resonance imaging show that responses to social rejection and physical pain share some common neuronal pathways, leading to a theory of ‘social pain’. This theory hypothesizes that the ‘pain’ of social rejection can be dampened by the endogenous opioids, particularly through the μ-opioid receptor (MOR) which alleviates physical pain, but is also known to regulate responses to social distress in several nonhuman species. To test this hypothesis in humans, we used a MOR radiotracer to measure changes in MOR binding potential (that is, in vivo receptor availability) with positron emission tomography during social feedback. We found that social rejection as well as acceptance activated the MOR system above baseline in different brain regions, showing that the endogenous opioid system responds to social feedback in humans. (a) Social rejection shown here activated the MOR system in the left amygdala. (b) Activation levels extracted from the left amygdala were positively correlated with the personality trait resiliency, suggesting that during rejection high-resilient individuals are more capable of MOR activation, which may be protective or adaptive. For more information on this topic, please refer to the article by Hsu et al. on pages 1211–1217.