Extinction—defined as the gradual disappearance of a learned response following the withdrawal of reinforcement—was first described by Pavlov (1927), and has been a subject of great psychological and neurobiological interest for a number of decades. Extinction is a fundamental learning process that has also formed the basis of prolonged exposure treatments for mental health disorders, including post-traumatic stress disorder and phobia, but potentially also for addictions. However, prolonged exposure therapy is not effective for all patients. Advances in understanding the psychopharmacology of extinction, at the whole-organism and circuit levels, are directing us to novel ways for optimising therapy-based around extinction. It is increasingly providing us with novel insights into the basic process itself. Preclinical research is also helping to address the underlying mechanisms and clinical feasibility of interventions such as exploiting memory updating mechanisms by extinguishing a memory within a critical window of reconsolidation.