Negotiations on the establishment of a Middle East zone free of biological, nuclear, and chemical weapons and their means of delivery are now at a critical phase after more than three decades of prenegotiations. This article examines the factors that have impeded negotiations in order to identify the key actors whose mutually reinforcing efforts are essential to its establishment. We argue that current efforts to negotiate a zone free of nuclear weapons and other weapons of mass destruction and their delivery systems (WMDFZ) in the Middle East can learn much from the successful negotiation of other nuclear weapons free zones (NWFZs). Nevertheless, the circumstances in the Middle East are unique and require a more holistic approach. Success here will depend largely on a multidimensional perspective that brings together the energies and insights of a range of state and nonstate actors, not least civil society in the Middle East, where confidence and trust building is too complex and demanding a task to be seen as the preserve of political and geostrategic calculation. Enabling the societies and polities of the region to identify areas of mistrust and misunderstanding across strategic, political, but also cultural and religious divides in order to open up possibilities for dialogue and mutual respect holds the key to creating a favorable negotiating environment.