Recognizing the highly nonlinear and coupled nature of chemical reaction mechanisms of relevance to combustion, and that realistic combustion situations frequently involve extensive variations in the system pressure as well as the local temperature and composition, it is advocated that development of detailed and simplified reaction mechanisms should strive for comprehensiveness in their coverage in terms of thermodynamic parameters, combustion phenomena, and fuel hierarchy. The possibility of mechanism simplification without sacrificing comprehensiveness is demonstrated for a detailed ethylene oxidation mechanism that consists of 70 species and 463 elementary reactions. It is shown that this detailed mechanism can be first simplified, through application of the directed relation graph, to a skeletal mechanism that consists of only 33 species and 205 elementary reactions. This skeletal mechanism is then further simplified to a reduced mechanism that consists of only 21 species and 16 lumped reactions, obtained by assuming quasi-steadiness for species identified through computational singular perturbation. It is further demonstrated that these two mechanisms mimic closely and comprehensively the detailed mechanism for the homogeneous phenomena of perfectly stirred reactor and auto-ignition, and diffusive phenomena of the laminar flame speeds and counterflow ignition, over extensive variations in terms of the system pressure, temperature, and composition.