Self-injury is a common and intransigent behaviour for many individuals with intellectual disability. Operant learning models and their derived interventions continue to be the most effective and evidence-based approaches; however, they are often neglected in clinical practice. This review paper presents research delineating phenotype × environment interactions and suggests a developed model of self-injury to account for these interactions. Specifically, the influence of pain upon self-injury is discussed. In addition, the influence of impaired behavioural control on the development of self-injury is hypothesised.