Self-injurious behaviour is shown by a significant minority of children with developmental delay and has a substantial impact on child and carer wellbeing. Characteristics such as a greater degree of intellectual disability, autism spectrum disorder, some genetic syndromes and repetitive and impulsive behaviours are positively associated with self-injury. Prevalence generally increases with age into midadulthood and the behaviour is notably persistent. In this review, we discuss the dominant causal theory of self-injury which draws on the principles of operant learning. We evaluate the utility of this theory to account for all empirical observations of self-injury. A model of self-injury is presented that extends a previous model described by Guess and Carr. The new model integrates child characteristics and operant learning principles in a phenotype × environment paradigm to explain the variance in developmental trajectory of the severity of self-injury. Behaviour dysregulation, as evidenced by the associations between self-injury, self-restraint, repetitive and impulsive behaviours, is identified as potentially influencing the severity and persistence of self-injury. Risk markers for self-injury are identified and the extended model indicates points of intervention and highlights the possibility of risk-related, targeted early intervention. The need for increased training of practitioners in the delivery of demonstrably effective interventions for self-injury is identified.