The growing consumption of pharmaceuticals together with their incomplete removal in wastewater treatment plants (WWTPs) implies the occurrence of these compounds in natural water resources. To investigate the natural attenuation of selected pharmaceuticals (caffeine, acetaminophen, sulfamethoxazole, naproxen and carbamazepine) during vadose zone infiltration, unsaturated column (L 26.67 cm, Ø 7.62 cm) experiments, filled with a sandy-loamy soil, were performed using two input concentrations (100 and 1000 μg L−1). The software Hydrus 1D was used to simulate experimental data. Caffeine and acetaminophen were never detected at the column outlet indicating a low environmental concern. On the other hand, attenuation of the detected pharmaceuticals could be reproduced by a combination of retardation and removal approaches. Carbamazepine is among the selected contaminants the most persistent. A dependence of removal rates on input concentrations was detected for sulfamethoxazole (μw from 2.78 d−1 to 1.16 d−1) and naproxen (μw from 1.16 d−1 to 0.63 d−1) attributed mainly to decreased metabolism of microorganisms when a higher input concentration is applied. Two transformation products (TPs) (N4-Acetylsulfamethoxazole and epoxycarbamazepine) derived from sulfamethoxazole and carbamazepine transformation, respectively, were detected during the experiment with the highest input concentration.