Purpose– Clozapine is a well-known antipsychotic medication licensed for treatment-resistant schizophrenia, but there is limited research available to suggest its efficacy in the context of personality disorder and intellectual disabilities presenting with high-risk behaviour with or without psychotic symptoms. The purpose of this paper is to raise awareness of the benefits of using clozapine in patients with intellectual disabilities and personality disorder that present with a complex picture of serious risk of harm to both their life and the lives of others.Design/methodology/approach– The authors present five patients with intellectual disabilities and serious life-threatening challenging behaviour whom were started on clozapine as part of their multidisciplinary treatment plan to manage their presentation. The authors completed baseline assessment of five main symptom domains and then repeated this assessment following treatment with clozapine.Findings– In all five cases use of clozapine was objectively associated with an improvement in symptomatology, quality of life and a safe transfer to the community.Originality/value– The findings suggest that judicious use of clozapine could be considered as one of the effective pharmacological strategies in the management of patients with intellectual disabilities and personality disorder who present with serious life-threatening challenging behaviours.