Pain is a salient, aversive sensation which motivates avoidance, but also has a strong social signaling function. Numerous studies have shown that regions of the nervous system active in association with first-hand pain are also active in response to the pain of others. When witnessing somatic pain, such as seeing bodies in painful situations, significant activations occur not only in areas related to the processing of negative emotions, but also in neuronal structures engaged in somatosensation and the control of skeletal muscles. These empathy-related sensorimotor activations are selectively reviewed in this article, with a focus on studies using electrophysiological methods and paradigms investigating responses to somatic pain. Convergent evidence from these studies shows that these activations (1) occur at multiple levels of the nervous system, from the spinal cord up to the cerebral cortex, (2) are best conceptualized as activations of a defensive system, in line with the role of pain to protect body from injury, and (3) contribute to establishing a matching of psychological states between the sufferer and the observer, which ultimately supports empathic understanding and motivate prosocial action. Future research should thus focus on how these sensorimotor responses are related to higher-order empathic responses, including affective sharing and emotion regulation, and how this motivates approach-related prosocial behaviors aimed at alleviating the pain and suffering of others.