Occurrence of pharmaceuticals in the aquatic environment is nowadays a well-established issue that has become a matter of both scientific and public concern. Tons of different classes of pharmaceuticals find their way to the environment at variable degrees, after their use and excretion through wastewater and sewage treatment systems. The main goal of this study was to correlate the dynamics and the environmental risk of pharmaceuticals with different temporal and hydrological patterns, at the Guadiana Basin (South of Portugal). Water samples were collected bimonthly during 2017 (classified as a drought year) and 2018 (post-drought year) in: Zebro, Álamos and Amieira (intermittent hydrological streams), and Lucefécit (perennial hydrological stream). The pharmaceuticals quantified in higher concentrations, out of 27 investigated, were diclofenac (up to 4806 ng L-1), ibuprofen (3161 ng L-1), hydrochlorothiazide (2726 ng L-1) and carbamazepine (3223 ng L-1). Zebro and Álamos presented the highest contamination by this group of environmental hazardous substances, which may be correlated with the presence of wastewater treatment plants upstream the sampling point of each stream. Furthermore, the highest concentrations occurred mainly during the dry period (2017), when the flow was nearly inexistent in Zebro, and in Álamos after the first heavy rainfalls. In specific periods, the high concentrations of pharmaceuticals detected may induce risk for the organisms of lowest trophic levels, damaging the balance of the ecosystems at these streams. The risk quotient optimised approach (RQf) integrating exposure, toxicity and persistence factors, ranks the pharmaceuticals investigated in terms of risk for the aquatic ecosystems as follows: diclofenac, ibuprofen and carbamazepine (high risk), clarithromycin (moderate risk), acetaminophen, ofloxacin and bezafibrate (endurable risk), and hydrochlorothiazide (negligible risk).