Our understanding of chronic inflammatory and neuropathic pain at the molecular and cellular level has developed at an extraordinary rate in recent years. Inflammatory, or neuropathic, neuronal plasticity describes the process by which the neurons involved in pain transmission are converted from a state of normosensitivity to one in which they are hypersensitive. Here we summarize current theories on somatosensory neuroplasticity in a molecular context, highlighting key receptors, ion channels, and signal molecules involved. We also suggest new possibilities for drug design, based on the rational targeting of these molecular players.