We are amidst a global addiction crisis, yet stigmas surrounding addiction counterintuitively prevail. Understanding and appreciating the neurobiology of addiction is essential to dissolve this stigma and for the development of new pharmacological agents to improve upon currently narrow therapeutic options. This review highlights this and evaluates dopamine-and-cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) as a potential target to treat various forms of substance abuse. Despite the proven involvement of DARPP-32 in addiction pathophysiology, no robust investigations into compounds that could pharmacologically modulate it have been carried out. Agents capable of altering DARPP-32 signalling in this way could prevent or reverse drug abuse and improve upon currently substandard treatment options.