In this work, an overview of the excess enthalpies of binary mixture containing ionic liquid and molecular solvent is reported, taking into account the various structural features of both the ionic liquid and molecular solvent. Subsequently, the capability of the conductor-like screening model for real system (COSMO-RS) to predict the excess enthalpies of the binary system of ionic liquid and molecular solvent was further evaluated. In general, a good agreement between experimental excess enthalpies and COSMO-RS prediction was obtained. In addition, the COSMO-RS was able to depict and screen the type of molecular interaction that governs the excess enthalpies of ionic liquid and molecular solvent. Thus, COSMO-RS proved very useful as an a priori method that could be used as a tool in the selection or design of a suitable ionic liquid candidate for a certain task and application before extensive experimental measurement.