Pharmaceuticals remain in treated wastewater used to irrigate agricultural crops. Their effect on terrestrial plants is practically unknown. Here we tested whether these compounds can be considered as plant stress inducers. Several features characterize the general stress response in plants: production of reactive oxygen species acting as stress-response signals, MApKs signaling cascade inducing expression of defense genes, heat shock proteins preventing protein denaturation and degradation, and amino acids playing signaling roles and involved in osmoregulation. tomato seedlings bathing in a cocktail of pharmaceuticals (carbamazepine, Valporic acid, phenytoin, Diazepam, Lamotrigine) or in Carbamazepine alone, at different concentrations and during different time-periods, were used to study the patterns of stress-related markers. the accumulation of the stress-related biomarkers in leaf and root tissues pointed to a cumulative stress response, mobilizing the cell protection machinery to avoid metabolic modifications and to restore homeostasis. The described approach is suitable for the investigation of stress response of different crop plants to various contaminants present in treated wastewater. Expanding populations aggravates the demand for freshwater for human consumption, agriculture and industry. While the sources of freshwater are limited and often polluted, reclaimed wastewater offers an additional resource that could be used to irrigate crops in agricultural systems. However, only 1% of the water used for irrigation worldwide consists of treated wastewater. Several countries use reclaimed wastewater for crop irrigation. For example, Israel uses 85% of the treated wastewater for irrigation, over half of the total irrigation volume 1. However, the current water purification devices are unable to eliminate some pharmaceuticals used by humans for personal care and medicine, released in the sewage. With the growing use of treated wastewater for irrigation, increasing amounts of these products find their way in the agroecosystem 2. The fate of these pollutants on soils and on plants 3 , and the potential risks for humans ingesting the plant edible parts (from infants to pregnant women and seniors) are under scrutiny 4-6. Therefore, the use of treated wastewater in the EU could be regulated in the near future 7. Psychoactive drugs are a major class of pharmaceuticals still found after wastewater treatment 8,9. They originate from excretion by patients, discarded medications or pharmaceutical industry effluents. Among them, Carbamazepine (CBZ) is one of the most abundant. This drug is used to treat epilepsy and trigeminal neuralgia. Low removal efficiency and minimal degradability of CBZ and its metabolites have been reported 10,11. CBZ is detected in influent and effluent wastewater in municipal wastewater-treatment plants in many countries 10,12-14. For example, in the city of Peterbourg, ON, Canada, the concentration of CBZ and its derivatives was about 460 ng/l in the untreated wastewater and 440 ng/l after t...