This article compares and contrasts the Chemical, Biological, Radiological and Nuclear (CBRN) weapons programs of Al-Qaeda and Islamic State through the framework of organizational structure, typology, ideology and CBRN incidents (selected case studies). A three-step CBRN model explaining the use of CBRN weapons by both groups is proposed. This model suggests that the use of CBRN weapons is predicated on three factors: leadership at the strategic level; acquisition of material at the operational level and technical capabilities at the tactical level. It is found that the failure of both groups in developing and carrying out large-scale CBRN attacks boils down primarily to the lack of technical capabilities and the difficulties associated with acquisition of materials. It is argued that the future CBRN threat landscape will likely be dominated by the threat of small-scale, localized attacks using crude chemical or biological agents by lone actors or autonomous cells as opposed to larger-scale centrally directed attacks.