Recent reports of new pollution issues brought on by the presence of medications in the aquatic environment have sparked a great deal of interest in studies aiming at analyzing and mitigating the associated environmental risks, as well as the extent of this contamination. The main sources of pharmaceutical contaminants in natural lakes and rivers include clinic sewage, pharmaceutical production wastewater, and sewage from residences that have been contaminated by drug users' excretions. In evaluating the health of rivers, pharmaceutical pollutants have been identified as one of the emerging pollutants. The previous studies showed that the contaminants in pharmaceuticals that are widely used are non-steroidal anti-inflammatory drugs, antibiotics, antiretrovirals, and anticancer drugs. Additionally, this review demonstrated the use of analytical techniques to examine these contaminants in various kinds of River water. Due to their extremely low concentrations in the aqueous environment (about in the range of ng/L to g/L), it is necessary to apply a technique for highly sensitive and selective multicomponent simultaneous analysis to identify and quantify these products. This analytical technique provides a flexible and reliable means to identify and evaluate pharmaceutical contaminants in river water samples by combining solid phase extraction and hyphenated mass spectrometric techniques. SPE-LC/MS/MS is the main method for estimating the level of pollution.