Affiliative touch interactions are often rewarding. They can on one hand alleviate stress and negative affect, while on the other hand induce intense feelings of pleasure. The behavioral nature of touch interactions (e.g., soothing soft touch or rough-and-tumble play) is often very different depending on whether the motivation for touch is primarily relief of negative affect or social exploration and joy, which is guided by the individual’s underlying needs. Here we discuss the central neurochemistry involved in motivation for affiliative touch interactions, with a focus on the mu-opioid receptor (MOR) and oxytocin systems. While both of these neurochemical systems play critical roles in various aspects of social affiliation, there are inconsistencies regarding their specific role in driving motivation for social touch interactions. We discuss this in the light of test subjects’ motivational state (distress or comfort) and appraisal of the situational context, and propose that many of these apparent discrepancies can be resolved by accounting for these factors. © 2016 Springer Science+Business Media New York.