The aim of this study was the development of analytical methods for the simultaneous determination of 25 selected pharmaceuticals, metabolites, and pesticides, belonging to the various chemical classes, in river sediments and their corresponding surface and ground water with the purpose of monitoring the contamination levels. The methods were based on the solid-phase extraction as the sample preparation method for water samples, and the ultrasonic solvent extraction for the sediment samples, followed by the liquid chromatography-tandem mass spectrometry. High recoveries were achieved for extraction from both water and sediment samples for the majority of analytes. Low limits of detection were achieved for all investigated compounds in the water sample (1-5 ng L(-1)) as well as in the sediment (1-3 ng g(-1)). Applicability of the developed methods was demonstrated by determination of pharmaceutical and pesticide residues in 30 surface water, 44 groundwater, and 5 sediment samples from the Danube River Basin in Serbia. Sixty percent of target compounds were detected in environmental samples. The most frequently detected analytes in river sediments were the pesticides dimethoate and atrazine, while carbamazepine and metamizole metabolites 4-AAA and 4-FAA were the most frequently found in water samples.