The potential of laccase-mediator systems (LMS) for the removal and detoxification of two wastewater micropollutants, the antibiotic sulfamethoxazole (SMX) and the herbicide isoproturon (IPN), was assessed. The influence of various parameters on micropollutant oxidation rates, such as pH, mediator, enzyme and pollutant concentrations, was investigated with three mediators: 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), syringaldehyde (SA) and acetosyringone (AS). Both pollutants were completely transformed within a few hours in presence of laccase and ABTS, as well as, for SMX, in presence of AS or SA. The three mediators were consumed during the reaction (no catalytic reactions observed), at a ratio mediator/pollutant between 1.1 and 16 mol/mol. Faster oxidation kinetics were observed at lower pH values, but also higher mediator/pollutant ratios were required. Several transformation products were formed, including cross-coupled products. Product mixtures were always less toxic to algae than untreated pollutants. Finally, a kinetic model that could explain the experimental observations was established. Based on the findings in this study LMS appears to be a promising option to treat concentrated and potentially toxic industrial effluents.