A multiscale modeling study is reported on the adsorption of ethanol/water in five zeolitic-imidazolate frameworks (ZIFs) for biofuel purification. The ZIFs (ZIF-68, -69, -78, -79, and -81) have isoreticular Gmelinite topology but differ in organic linkers. The simulated adsorption isotherms of ethanol and water in ZIF-68 agree fairly well with experimental data. At a low pressure, ZIF-78 exhibits the highest uptake due to strong hydrogen-bonding between NO2 groups and adsorbates. The heats of adsorption at infinite dilution largely follow the trend of binding energies estimated from ab initio calculations. At a high pressure, the uptake is governed primarily by free volume but also affected by hydrogen-bonding. Among the five ZIFs, ZIF-79 with hydrophobic CH3 groups shows the highest adsorptive selectivity for ethanol/water mixtures. This study provides microscopic insights into the adsorption and separation of ethanol/water in ZIFs, and would facilitate the development of new ZIFs for biofuel purification. (c) 2015 American Institute of Chemical Engineers AIChE J, 61: 2763-2775, 2015