Nowadays, there is a pressing need to consolidate the scientific knowledge and to adopt the most suitable approaches to monitor the emerging pollutants in different water sources and wastewater and, at the same time, to assess the environmental risks and their action on the human health, as well as to prevent and control their disposal into the water sources and the environment. The emerging pollutants are represented in a broad sense by any synthetic or naturally-occurring chemical or any microorganism that is not commonly monitored in the environment with potentially known or suspected adverse ecological and human health effects. Among the main emerging pollutants that are incriminated for the adverse reactions are the pharmaceutical compounds and personal care products. Among these pharmaceuticals, antibiotics such as amoxicillin, cefuroxime, ciprofloxacin etc. are recognized as an emerging environmental contaminants class since these compounds have been massively administrated in humans and animals and usually persist in the environment through a complex vicious cycle of transformation and bioaccumulation. Another two classes of emerging pollutants are considered to be the endocrine disruptors and contraceptives which are compounds that may mimic or interfere with the function of hormones in the body. These substances may turn on, shut off, or modify signals that hormones carry, which may affect the normal functions of tissues and organs. With a focus on pharmaceuticals, a set of programs was initiated in the EU Member States in order to reduce the risks to human health and on the environment, including comprehensive monitoring programs. The Report of the Joint Danube Survey released in 2015, presented the contamination with pharmaceutical residues in water samples collected in August – September 2013 from 68 sites along the Danube River and the main tributaries. Other recent studies suggested a certain degree of contamination with pharmaceuticals in the Danube river basin, confirming the need for monitoring programs and future studies. However, according to the Directive 2013/39/EU amending Directive 2000/60/EC concerning the priority substances in thefield of water policy three compounds, diclofenac, 17 alpha ethinylestradiol, and 17 beta-estradiol were nominated in the first watch list (available from September 2014) to be studied within the EU-wide water monitoring framework. In the light of the new regulations and the concerns regarding the presence of pharmaceuticals in the water environment, the MONITOX project application form (May 31st, 2017) included as project goal the detection of selected compounds, such as antibiotics, anti-inflammatory, endocrine disruptors and contraceptives, in aquatic natural ecosystems located in the region of the Black Sea basin, Danube River and Danube Delta. The experimental design mainly consists in a solid-phase extraction (SPE) for the compound extraction and concentration followed by a high resolution mass spectrometry (HRMS) analysis using the Q-Exactive Orbitrapin both full scan (FS) and targeted ion fragmentation (tMS(2)) modes. The high resolution power of 70,000 (FWHM) of the Orbitrap technology enables the achievement of a high sensitivity and selectivity in the detection of compounds traces. A MS-MS confirmatory analysis for residues according to regulations (Decision 657/2000 and SANCO/12571/2013) is carried out with the same instrument. We expect that the results of the study will be considered for new implementation strategy in order to reduce the contamination due to pharmaceuticals. Acknowledgement: This work was supported by the project with code BSB27 MONITOX, contract grant 105070/14.09.2018.