Cytostatics are a major class of chemotherapy drugs with great potential to cause genotoxic and/or mutagenic effects in all organisms. Currently, hospital wastewater treatment systems (HWTS) are not able to remove these compounds and they are discharged to the environment. Thus, the objective of this study was to investigate the oxidative degradation of the cytostatic drugs doxorubicin (DOXO) [(8s,10s)-10-(4-amino-5-hydroxy-6-methyl-tetrahydro-2h-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione] and methotrexate (METHO) {N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid} by ozonolysis alone and using a combined sonolysis/ozonolysis process on bench-scale at different pH values. Besides determining the degradation efficiency, a kinetic approach was applied to determine the reaction order and rate constants for different oxidative processes carried out at pH 7.0, which is the normal pH of hospital wastewater. The results showed that the removal efficiency of these compounds is pH-dependent. A combination of sonolysis and ozonolysis processes is more efficient than the ozonolysis process alone for the degradation of doxorubicin at all pH values, while methotrexate can easily be degraded by ozonolysis alone or sonolysis/ozonolysis methodologies at any pH.