Israel began its nuclear weapons program in 1958. Ever since the state of Israel has pursued a consistent policy of nuclear ambiguity, and has amassed over time a huge nuclear arsenal. The United States, as Israel’s strategic ally, and despite some initial misgivings in the early 1960s, has actively supported this policy of nuclear ambiguity. Faced with such a situation, other countries in the region have tried, since 1963, to work towards the establishment of a nuclear- and WMD-free Middle East, which has failed to materialize up to now. The present article looks into the development of the nexus between the Israeli nuclear ambiguity policy and regional efforts towards the establishment of a nuclear- and WMD-free Middle East. The article will discuss the rationale of the Israeli outlook and policy and their implications and repercussions for the countries in the region, and the region at large. The article argues that the Israeli nuclear policy and the categorical refusal to join the NPT have as a matter of fact served as a source of national security threat for others in the region, led some to seek to acquire nuclear capability, and forced arms race on a regional scale. The article concludes that issues of interest and concern to all the parties involved would, in the final analysis, have to be addressed within the context of and in relation to other issues, including in particular, the nexus between regional peace and the nuclear issue. The authors’ final conclusion is that meaningful movement in such a direction will require and depend on the emergence of a realistic outlook on the part of all parties concerned.