Noxious stimuli cause pain and pain arises from noxious stimuli… usually. Exceptions to these apparent truisms are the basis for clinically important problems and provide valuable insight into the neural code for pain. In this Perspective, we will discuss how painful sensations are encoded. We will argue that although primary somatosensory afferents are specialized (i.e. tuned to specific stimulus features), natural stimuli often activate >1 type of afferent. Manipulating co-activation patterns can alter perception, which argues against each type of afferent acting independently (as expected for strictly labeled lines) and suggests instead that signals conveyed by different types of afferents interact. Deciphering the central circuits that mediate those interactions is critical for explaining the generation and modulation of neural signals ultimately perceived as pain. The advent of genetic and optical dissection techniques promise to dramatically accelerate progress towards this goal, which will facilitate the rational design of future pain therapeutics.