This article provides a critical overview of the key commercial, technical, legal, and political challenges the Eastern Mediterranean region faces in regard to the development of its natural gas resources and proposes possible ways to overcome them. To that aim, it first gives an up-to-date overview of the upstream developments in the region. It then discusses the challenges facing the monetization of the gas discoveries by looking at both the commercial challenges hampering exploration and field development and the technical challenges involved in exporting the gas to the immediate and distant markets. While examining the legal and political challenges related to maritime delimitation and political alignments, it highlights the role of gas. Finally, it offers some possible ways to overcome those challenges.