Objectives: This review aimed at presenting the mechanisms and pitfalls of adhesion to enamel and dentin, advances in the materials science and in the development of strategies to improve hybrid layer (HL) longevity. Methods: Search of the literature was performed on PubMed, Scopus and Web of Science with keywords related to the structure of the dental substrate, HL degradation mechanisms and strategies to contrast them. Results: Albeit the advances in the dental materials’ properties, HL degradation is still a relevant and current issue in adhesive dentistry. However, adhesive materials have become more resistant and less operator sensitive, and good adhesion is currently in the hands of every practitioner. Numerous novel strategies are being developed, able to improve the resistance of adhesive resins to degradation, their ability to infiltrate and chemically bond to dentin, to remove the unbound/residual water within the HL, reinforce the dentin collagen matrix, and inhibit endogenous metalloproteinases. Many of the strategies have turned to nature in search for powerful biomodifying compounds, and for the inspiration as to mimic naturally occurring regenerative processes. Significance: Extensive knowledge on the structure of the dental substrate and the complexity of adhesion to dentin has led to the development of improved formulations of dental adhesives and numerous valid strategies to improve the strength and longevity of the HL. Nevertheless, for many of them the road from bench to chairside still seems long. We encourage practitioners to know their materials well and use the strategies readily available to them.
