Emerging pollutants such as pharmaceuticals have been focusing international attention for a few decades. Ciprofloxacin (CIP) is a common drug that is widely found in hospital and wastewater treatment plants effluents, as well as in rivers. In this work, the feasibility of CIP degradation by ultrasound process at high frequency is discussed and sonolysis, sonolysis with hydrogen peroxide and sono-Fenton are evaluated. The amounts of hydrogen peroxide and ferrous ions (Fe 2+) needed were optimized using response surface methodology. Best results were obtained with the sono-Fenton process resulting in a total pharmaceutical degradation within 15 minutes and a mineralization greater than 60% after one hour. Optimal conditions were tested on a real matrix from a municipal wastewater treatment plant. Even if the degradation of the pollutants by sono-Fenton was hampered, the removal efficiency of both CIP and total organic carbon (TOC) is interesting as an increase in the biodegradability of the wastewater is found. These results show that sono-Fenton oxidation can be a promising pre-treatment process for pharmaceutical-containing wastewaters.