Pain is not a single entity but is instead a collection of sensory experiences commonly associated with tissue damage. There is growing recognition that not all pains are equivalent, that pains and pathologies are not related in a simple manner, and that acute pains differ in many respects from persistent pains. Great strides have been made in improving our understanding of the neuronal mechanisms responsible for acute pain, but the studies leading to these advances have also led to the realization that a bewildering array of processes are interposed between tissue damage and sensations of pain, especially in persistent pains. Persistent pains often seem unrelated or disproportionate to identifiable pathology, and they are modulated by a multitude of factors. This complexity in such a vital function serves as a challenge both to scientists seeking fundamental understanding and to clinicians faced with the immediate need to treat patients with painful disorders.