Abstract The Paleozoic section became prospective during the early 1970s when the enormous gas reserves in the Permian Khuff reservoirs were delineated in the Gulf and Zagros regions and oil was discovered in Oman. Since then, frontier exploration has targeted the Paleozoic System throughout the Middle East, driven by the need to replace oil production from maturing fields, the need to add gas reserves to meet local energy requirements, and other economic considerations. The Paleozoic sequences were essentially deposited in continental to deep-marine siliciclastic environments at the Gondwana continental margin. Carbonates became dominant only in the Late Permian. The sediments were deposited in arid to glacial settings, reflecting the drift of the region from equatorial to high southern latitudes and back. Following late Precambrian rifting that formed salt basins in Oman and the Arabian Gulf region, the Cambrian-Ordovician sequences were deposited on a peneplained continental platform. However, by the Late Ordovician, this margin probably differentiated into two terranes along the Zagros fault zone, as indicated by the Silurian paleogeography. The entire region was affected by the Hercynian orogeny during the Carboniferous, which caused long-wavelength plate buckling in the north, block uplifts in the central region and regional uplift in the south, and tectonism along the Zagros fault zone. This deformation caused widespread erosion of the Devonian-Carboniferous section, and probably was caused by collision along the northern margin of Gondwana. The Paleozoic tectonic supercycle ended with the onset of breakup tectonics in the Permian and deposition of Khuff carbonates over the eastern passive margin. A major Paleozoic petroleum system embraces reservoir seal pairs spanning the Silurian to Permian sequences. Hydrocarbons occur in a variety of traps and are sourced primarily by the Silurian “hot” shale. Hydrocarbon expulsion estimates (taking into account secondary migration losses) suggest that about 1 trillion barrels of oil equivalent may have been trapped from the Silurian “hot” shale alone. A second petroleum system occurs in areas charged from Upper Precambrian source rocks in salt basins. Problems with deep seismic imaging and relatively tight and heterogeneous reservoirs, combined with hostile subsurface environments, pose significant challenges to exploration and development. The critical success factor is the continuous innovative effort of earth scientists and subsurface engineers to find integrated technology solutions which render the Paleozoic plays economically viable even in a low-oil-price environment.