The sealing ability of restorations is an important factor in order to prevent or reduce marginal gaps, which are often associated with postoperative sensitivity, caries and pulp disease. Usually the sealing ability of a new material is tested under laboratory conditions before being introduced on the market. However, in vitro evaluation of marginal integrity cannot predict in vivo performances of enamel-dentin bonding systems. A critical review of available data on sealing ability of last generation of adhesive-restorative materials placed on vital teeth is presented. The review includes the data of sealing performances of direct and indirect restorations, ethical considerations, influence of dental substrates on bonding, correlation between in vivo leakage studies and bond strength tests and microscopic evaluations. An in vivo protocol is presented in order to standardize leakage studies performed on vital teeth. A larger number of in vivo leakage tests are desirable in order to compare properties of new materials in multicenter studies. The ideal sequence of evaluation for new enamel-dentin bonding systems should be: in vitro tests, short term in vivo evaluations and then clinical trials.