Israel is a notable outsider from the NPT regime. The issue of Israel's non-adherence to the NPT has been raised repeatedly by other Middle Eastern NPT states at review conferences, which convene every five years to assess implementation of the treaty. By the time of the 2000 Review Conference, Israel was the only state in the Middle East that had not joined the treaty. Israel has responded that acceptance of the NPT, or equivalent treaty undertakings, is dependent upon achievement of a comprehensive peace in the region, and the renunciation of other forms of WMD by all Middle Eastern states.

On September 6, 2007, Israel conducted an air strike against a site in the Syrian Desert, hitting a facility near the Euphrates River. Israel and American intelligence analysts hypothesized that the destroyed facility had been an unfinished nuclear reactor. U.S. intelligence sources confirmed this ascertain during a press briefing in April 2008. The officials elaborated that the reactor was based on a North Korean design, was incomplete at the time of the air strike, and had not been loaded with nuclear materials. IAEA officials have expressed displeasure that Israel and the United States failed to provide the agency with intelligence of Syria’s nuclear reactor activities before the September air strike. The IAEA officials have stated that a lack of available evidence on Syria’s nuclear activities precluded IAEA action in the matter, arguing in a June 2008 press release that Israel’s unilateral strike “undermin[ed] the due process of verification that is at the heart of the non-proliferation regime.”