The 2015 NPT Review Conference failed to agree on a Final Document. Non-proliferation experts perceived the trend as very worrying one witnessing to impossibility of the NPT member states to achieve a consensus on the issue. Moreover, the trend in experts’ view jeopardizes the very non-proliferation regime. Taking a political constructivist and regime theories approaches, the paper deals with challenges the non-proliferation regime faces today. The research shows that the NPT regime is transforming internally, externally, and in the context of balance of power shift at a global level. Being formed in the 1970s, the non-proliferation regime is being tested by new actors, regional non-nuclear communities, and changes in the global distribution of power. The classical two-level system the power is distributed within (between nuclear and non-nuclear states) is followed by a multi-level complexity of interests and ambitions.