According to the ICD-11 (World Health Organization, 2019), substance use disorders include disorders that result from a single occasion or repeated use of substances (both legal and illegal) that have psychoactive properties; all drugs that are taken in excess have in common direct activation of the brain reward system, which is involved in the reinforcement of behaviours and the production of memories. They produce such an intense activation of the reward system that normal activities may be neglected. Instead of achieving reward system activation through adaptive behaviours, drugs of abuse directly activate the reward pathways. The pharmacological mechanisms by which each class of drugs produces reward are different, but the drugs typically activate the system and produce feelings of pleasure, often referred to as a ‘high’ (American Psychiatric Association, 2013). This chapter will cover all substance use in people with intellectual disability, whether it is a problem, and alternative treatments.