Although people often describe experiences of social rejection as being “painful,” one is left to wonder whether these descriptions are primarily metaphorical or whether there is something truly painful about rejection experiences. This chapter reviews accumulating evidence showing that social pain—the painful feelings following social rejection, exclusion, or loss—relies on some of the same neural circuitry that is involved in processing physical pain. Moreover, building on this overlap in the neural circuitry underlying physical and social pain, this chapter reviews several consequences of this shared circuitry. Specifically, evidence is reviewed to show: (1) that individuals who are more sensitive to one kind of pain are also more sensitive to the other and (2) that factors that typically alter one type of pain (e.g., Tylenol reduces physical pain) can alter the other as well (e.g., Tylenol reduces social pain). Other possible consequences of this shared neural circuitry are discussed.