Target compound monitoring is often not sufficient to assess the quality of water, as many of the unknown micro-contaminants present might be a threat to the environment and human health. In this work, the potential of hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS) coupled to liquid chromatography (LC) in the elucidation of unknown compounds in environmental water samples has been explored. Based on accurate mass measurement, possible elemental compositions for the precursor ions were calculated. Using model compounds, a useful strategy was developed, enabling determination and evaluation of potential molecular formulae for the detected unknowns. The possibility of performing tandem mass spectrometric (MS/MS) acquisitions to obtain product ion spectra in accurate mass mode also helped to elucidate the structures of these unknowns or to detect some functional groups, to further evaluate potential formulae. The remaining formulae were searched against available databases such as the Merck Index and the NIST library. Where standards were commercially available, retention time and MS/MS data were both also used as confirmatory tools. The approach developed was applied for the identification of unknown compounds in different types of water. To improve sensitivity, environmental water samples were preconcentrated on-line in a polymeric cartridge by direct injection of 2 mL water into the SPE-LC/MS/MS system. For three unknowns, structures were proposed and confirmed with standards. Although other compounds could not be unequivocally identified based on the data available within this study, details about the possible structures of some are given.