Hydrophilic interaction chromatography (HILIC) is a relatively recently introduced mode of liquid-phase separations. Recently, HILIC has been used for coupling to MS in metabonomic/metabolomic studies to provide a complementary tool to the widely used reversed-phase (RP) chromatographic separations. The combination of HILIC with MS detection covers a number of polar metabolites that are typically nonretained in RPLC-mode separations and thus enlarging the number of detected analytes. This way of metabolite profiling thus provides more comprehensive metabolome coverage than using RP chromatography alone. This review describes the applications and the utility of HILIC-MS in metabolomic/metabonomic studies and highlights certain characteristic examples in the life and plant-food sciences.