The immediate bonding effectiveness of contemporary adhesives is quite favorable, regardless of the approach used. In the long term, the bonding effectiveness of some adhesives drops dramatically, whereas the bond strengths of other adhesives are more stable. This review examines the fundamental processes that cause the adhesion of biomaterials to enamel and dentin to degrade with time. Non-carious class V clinical trials remain the ultimate test method for the assessment of bonding effectiveness, but in addition to being high-cost, they are time- and labor-consuming, and they provide little information on the true cause of clinical failure. Therefore, several laboratory protocols were developed to predict bond durability. This paper critically appraises methodologies that focus on chemical degradation patterns of hydrolysis and elution of interface components, as well as mechanically oriented test set-ups, such as fatigue and fracture toughness measurements. A correlation of in vitro and in vivo data revealed that, currently, the most validated method to assess adhesion durability involves aging of micro-specimens of biomaterials bonded to either enamel or dentin. After about 3 months, all classes of adhesives exhibited mechanical and morphological evidence of degradation that resembles in vivo aging effects. A comparison of contemporary adhesives revealed that the three-step etch-and-rinse adhesives remain the 'gold standard' in terms of durability. Any kind of simplification in the clinical application procedure results in loss of bonding effectiveness. Only the two-step self-etch adhesives approach the gold standard and do have some additional clinical benefits.