Recent advances on biomarker research are discussed, primarily relying on experience gained with technologies based on liquid chromatography-tandem mass spectrometry (LC-MS-MS). Determination of urinary metabolites of industrial chemicals (n-hexane, benzene, toluene, and styrene) in samples from occupationally exposed workers and controls was performed by LC-MS-MS with either electrospray (ESI) or atmospheric pressure chemical ionization (APCI), as appropriate. Both phase I and II metabolites (glucuronides, sulfates, and mercapturic acids) can be detected with little or no sample manipulation, thus allowing the identification of a number of artifacts and "new" metabolites. However, experimental evidence indicates the need for properly addressing the matrix effect, which is always associated with the analysis of biological samples. Both efficient sample preparation and the use of isotopically labeled internal standards seem to be necessary to develop validated quantitative methods.