Cytochrome P450 (CYP) enzymes represent a superfamily of hemoproteins that are involved in the metabolism of a wide variety of endogenous and exogenous compounds. For a given CYP enzyme, kinetic properties of a substrate are usually related to substrate lipophilicity (log P or log D7.4). In this review, enzyme kinetic parameters (Km, Vmax, and Vmax/Km) of 215 CYP3A4-mediated metabolic reactions of 113 drugs in human liver microsomes were obtained from the literature, and lipophilicity values of the 113 drugs were calculated using the ACD/Labs 8.0 program. A low degree of Km- or (Vmax/Km)-lipophilicity correlation, but no Vmax-lipophilicity correlation, is exhibited for the CYP3A4-mediated reactions. Overall, Km decreases, but Vmax/Km increases, with increasing substrate lipophilicity, and Vmax appears to be independent of substrate lipophilicity. In other words, a low Km generally confers a high Vmax/Km ratio for a substrate. The degree of lipophilicity-kinetics correlations is related to both reaction types (or reaction mechanisms) and regiochemical positions (or physicochemical properties) of the reaction groups of the substrates. Among the categorized CYP3A4- mediated reactions, the best lipophilicity-kinetics correlation is achieved for carbon hydroxylation, followed by Ndealkylation. No or little lipophilicity-kinetics correlations are seen for N, S-oxidation and other reactions. Within the hydroxylation group, aliphatic hydroxylation shows the best lipophilicity-kinetics correlation while hydroxylation on a carbon atom adjacent to an aromatic ring does not show any lipophilicity-kinetics correlation. The detailed structural and kinetic data sets of the human liver microsomal CYP3A4-mediated reactions represent a specialized database useful for researchers working in the area of structure-metabolism relationship modeling and analysis.