Both ecosystem and human health rely on clean, abundant supplies of water, thus many classes of potential pollutants are regulated. In recent years, the possible risks associated with largely uncontrolled inputs of pharmaceuticals to rivers, lakes, groundwater, and coastal waters, mainly via wastewater, have been a focus of much research. During this time, our capacity to sequester, identify, and quantify pharmaceuticals in environmental matrices has improved. Devices have emerged to allow passive uptake of drugs to augment or replace laborious grab sampling. Advances in sample preparation have streamlined extraction procedures and removed interfering matrix components. New instrumental techniques have allowed faster, more accurate and sensitive detection of drugs in water samples. This review highlights all of these advances, from sample collection to instrumental analysis, which will continue to help us better understand the fate and effects of pharmaceuticals in aquatic systems.