Substance abusers make many bad decisions for the short-term satisfaction of a "high," at the cost of various undesirable longer-term consequences—withdrawal symptoms; physical and mental abuse and their associated medical and psychiatric complications; loss of family, friends, money, and employment; legal prosecution and incarceration; and sometimes death. Their ability to make better decisions is further impaired by a triad of relapse precipitants: drug-related cues, small amounts of the drug itself (called priming), and various types of stress. These precipitants are readily modeled in animals and have been precisely quantified and understood through elegant neurobiological experiments (1, 2). The neurobiological framework for understanding animal reinstatement models for human relapse to addiction has explicated mechanisms ranging from neuroanatomical pathways to neurotransmitters to second-, third-, and fourth-level intraneuronal messengers and the associated gene activations induced by acute and chronic drug self-administration (3). Insights generated from this extensive neurobiology, which has been developing over the past 40 years, are driving translational studies that advance our knowledge further still. The new translational studies are taking our clinical observations about protracted withdrawal and providing them with a biological basis that can have direct pharmacotherapeutic applications in preventing relapse to addiction after the acute withdrawal syndromes have been treated and have abated (4, 5). Like the best of transformative clinical research in psychiatry, these studies link biological probes with behavioral outcomes and interventions.