The photocatalytic degradation of caffeine has been investigated in aqueous suspensions of titanium dioxide (TiO₂) by monitoring process efficiency at varying TiO₂ (25 - 175 mg l^-1) and initial drug concentrations (0.5 - 9.5 mg l^-1). The use of the response surface methodology (RSM) allowed to fit the optimal regions of the parameters leading to the degradation of the pollutant. Also, a single polynomial expression modelling the reaction was obtained. In parallel a set of bioassays (Daphnia magna, Pseudokirchneriella subcapitata and Lactuca sativa) was performed to evaluate the process in terms of detoxification of caffeine oxidation by-products under chronic and acute tests. Results clearly demonstrate that caffeine is quickly degraded, but not mineralized as quickly, and that persistent toxic organic intermediates resist further oxidation.