Misuse of novel psychoactive substances, also known as legal highs, is growing in the UK. These substances include more than 200 psychoactive chemicals and are associated with harm to physical and mental health, but are not controlled under the Misuse of Drugs Act 1971 or regulated as a medicine. This article reviews the evidence relating to psychosocial interventions for illegal substance misuse to identify how therapies could improve rates of abstinence and awareness in adults who are misusing novel psychoactive substances. The evidence is limited and there is a need for further research and increased awareness among health professionals and the general population of this growing problem.