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SPE Journal: 2021 SPE Reservoir Simulation Conference Special Issue This special issue in SPE Journal presents selected and peer-reviewed versions of technical papers presented at the, which is the 26th meeting in the conference series. The papers represent a cross section of contemporary research and cover a wide range of topics, from research on basic discretization schemes, solution strategies, and optimization methods, to uncertainty quantification, fractured unconventionals, machine-learning methods, and implementations on last generation multicore architectures. An overview paper will also be included, which will celebrate the 25 previous conferences by reflecting on the past 60 years of reservoir simulation. The issue will be built live as papers are accepted for publication in SPE Journal and compiled on onepetro.org. The papers represent a cross section of contemporary research and cover a wide range of topics, from research on basic discretization schemes, solution strategies, and optimization methods, to uncertainty quantification, fractured unconventionals, machine-learning methods, and implementations on last generation multicore architectures.