Bonding to tooth tissue can be achieved through an "etch&rinse," "self-etch" or "glass-ionomer" approach. In this paper, the basic bonding mechanism to enamel and dentin of these three approaches is demonstrated by means of ultramorphological and chemical characterization of tooth-biomaterial interfacial interactions. Furthermore, bond-strength testing and measurement of marginal-sealing effectiveness (the two most commonly employed methodologies to determine "bonding effectiveness" in the laboratory) are evaluated upon their value and relevance in predicting clinical performance. A new dynamic methodology to test biomaterial-tooth bonds in a fatigue mode is introduced with a recently developed micro-rotary fatigue-testing device. Eventually, today's adhesives will be critically weighted upon their performance in diverse laboratory studies and clinical trials. Special attention has been given to the benefits/drawbacks of an etch&rinse versus a self-etch approach and the long-term performance of these adhesives. Correlating data gathered in the laboratory with clinical results clearly showed that laboratory research CAN predict clinical effectiveness. Although there is a tendency to simplify bonding procedures, the data presented confirm that conventional three-step etch&rinse adhesives still perform most favorably and are most reliable in the long-term. Nevertheless, a self-etch approach may have the best future perspective. Clinically, when adhesives no longer require an "etch&rinse" step, the application time, and probably more importantly, the technique-sensitivity are substantially reduced. Especially "mild," two-step self-etch adhesives that bond through a combined micromechanical and chemical interaction with tooth tissue closely approach conventional three-step systems in bonding performance.