Mass spectrometry (MS) coupled to chromatography has been increasingly used in the environmental field, as it allows the best performance currently attainable for the investigation of a wide range of organic pollutants. When dealing with emerging contaminants, there is a clear trend towards the use of liquid chromatography-mass spectrometry (LC-MS) techniques, from tandem (low-resolution) MS to high-resolution (HR) MS. HRMS allows targeted and untargeted analysis, thanks to full-spectrum acquisition at high mass accuracy with good sensitivity. With the same instrument, target, suspect and non-target screening can be performed, as can retrospective analysis and discovery of transformation/degradation products. This article gives a general overview on the use of HRMS in LC-based methods directed towards the investigation of illicit drugs and pharmaceuticals in the aqueous environment. We consider time-of-flight and Orbitrap mass analyzers, and we discuss the benefits of using ultra-high-performance liquid chromatography (UHPLC) in combination with HRMS. ; Plan Nacional de I+D+I, Ministerio de Economia y Competitividad. CTQ2012-36189 Generalitat Valenciana (Group of Excellence Prometeo). 2009/054 Generalitat Valenciana (Collaborative Research on Environment and Food Safety). ISIC/2012/016