We discuss and develop an entropy-driven principle for separating isomers of alkanes in the five to seven carbon atom range by adsorption on silicalite-1. The normal alkanes are preferentially adsorbed because of configurational entropy effects; they “pack” more efficiently within the channel structures of silicalite. To demonstrate the separation principle we carried out CBMC simulations to determine the isotherms of various mixtures of linear and branched alkanes in silicalite-1. We show that the configurational entropy effects manifest at loadings greater than 4 molecules/unit cell and the sorption favors the linear alkanes while the branched alkanes are virtually excluded from the silicalite matrix. Validation of the entropy-based separation principle is obtained by analyzing the silicalite membrane permeation data published in the literature.