The aim of this study was to investigate the degradation of hydrogels that degrade through different mechanisms. As models, two types of dextran-based hydrogels were investigated. Dextran methacrylate (dex-MA) hydrogels that are degraded by entrapped dextranase were used as a model for hydrogels that degrade by hydrolysis of the polymer backbone. Dextran hydroxyethyl methacrylate (dex-HEMA) hydrogels were used as a model for hydrogels that degrade by hydrolysis of the cross-links. The degradation was characterized theologically and analytically by determination of the degradation products and by the swelling behavior of the hydrogels. The degradation kinetics as observed from the various characterization techniques were distinctively different and depended on both the composition of the hydrogels and the degradation mechanism. Combining all the results, a qualitative understanding could be proposed for the degradation of the polymer networks of both types of hydrogels. The insight obtained can help the development of degrading hydrogels for specific applications and the choice of a suited technique for evaluation of the degradation.