The photolysis of diclofenac (DCF), sulfamethoxazole (SMX), carbamazepine (CBZ), and trimethoprim (TMP) was investigated using a low-pressure (LP) mercury ultraviolet (UV) lamp (254 nm) and a combination of UV with hydrogen peroxide (H2O2). For each experiment, 5 mg/L of each pharmaceutical was prepared in pure water and individually degraded by either UV alone or UV/H2O2. DCF and SMX were highly susceptible to UV treatment and completely degraded to below their LC–MS detection limit (1 μg/L) after only 8 min of UV irradiation. TMP and CBZ were more resistant to UV treatment, with only 58.2 and 25.2% degradation (after 1 h UV exposure). The combination of H2O2 addition (up to 0.2 g/L) with UV significantly improved the removal rate of TMP and CBZ up to 91.2 and 99.7% of the initial concentration, respectively. A number of novel transformation compounds were identified as UV or UV/H2O2 degradation products using LC–MS. The range and amount of these transformation compounds strongly depended on the applied treatment conditions. The toxicity of each pharmaceutical solution before and after treatment was also evaluated and all parent compounds were non-toxic at the tested concentration (i.e. 5 mg/L). DCF, in particular, but also CBZ and SMX, showed an increase in solution toxicity after treatment with UV only, indicating the presence of photolytic degradation products that are more toxic than the parent compounds. Treatment with UV/H2O2 reduced the toxicity of all solutions to below the detection limit of the assay.