Drug addiction has been defined as a chronically relapsing disorder that is characterized by a compulsion to seek and take a drug or stimulus, the loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug or stimulus is prevented, a component of which is anhedonia. The present review explores a heuristic framework for understanding the role of anhedonia in addiction, in which anhedonia is a key component of hyperkatifeia (conceptualized as the potentiated intensity of negative emotional/motivational symptoms during drug withdrawal) and negative reinforcement in addiction. The neural substrates that mediate such anhedonia and crosstalk between elements of hyperkatifeia that contribute to anhedonia are then explored, including crosstalk between physical pain and emotional pain systems. The present review explores current knowledge of neurochemical neurocircuitry changes that are associated with conditioned hyperkatifeia/anhedonia. The overall hypothesis is that the shift in motivation toward negative reinforcement in addiction reflects the allostatic misregulation of hedonic tone, such that drug taking makes anhedonia worse during the process of seeking temporary relief by compulsive drug taking, thereby perpetuating the addiction cycle and hedonic comorbidities that are associated with addiction.