Shoulder pain is often a challenging clinical phenomenon because of the potential mismatch between pathology and the perception of pain. Current evidence clearly emphasizes an incomplete understanding of the nature of shoulder pain. Indeed, the effective diagnosis and treatment of shoulder pain should not only rely upon a detailed knowledge of the peripheral pathologies that may be present in the shoulder, but also on current knowledge of pain neurophysiology. To assess and treat shoulder pain, a comprehensive understanding of the way in which pain is processed is essential. This review reflects modern pain neurophysiology to the shoulder and aims to answer the following questions: why does my shoulder hurt? What is the impact of shoulder pain on muscle function? What are the implications for the clinical examination of the shoulder? And finally, what are the clinical implications for therapy? Despite the increasing amount of research in this area, an in-depth understanding of the bidirectional nociception-motor interaction is still far from being achieved. Many questions remain, especially related to the treatment of nociception-motor interactions.