Background The increase in the prevalence of aortic stenosis due to an aging population has led to an increasing number of surgical aortic valve replacements. Over the past 20 years, there has been a major shift in preference from mechanical to bioprosthetic valves. However, despite efforts, there is still no “ideal” bioprosthesis. It is crucial to understand the structure, biology, and function of native heart valves to design more intelligent, strong, durable and physiological heart valve tissues. Methods A comprehensive review of the literature was performed to identify articles reporting the basic mechanisms of bioprosthetic valve dysfunction and the biology of native valve cells. Searches were run in PubMed, MEDLINE® and Google Scholar. Search terms included subject heading and keywords for the following terms: “biological heart valve dysfunction”, “bioprosthesis dysfunction”, “bioprosthesis degeneration” and “tissue heart valves” Results All the relevant findings are summarized in specific illustrations and tables within the appropriate subsections. Structural dysfunction is a logical and expected consequence of the chemical, mechanical and immunological processes that occur during fixation, manufacture, and implantation. Conclusion Biological prosthesis valve dysfunction is a clinically significant process. It has become a major issue considering the growing rate of bioprosthesis implantation and improved long-term patient survival. Research on the field has improved in the past few years but there is still not an ideal bioprosthesis. Understanding bioprosthetic aortic valve degeneration from a basic science perspective is a key point to improve technologic advances and specifications that lead to new generation of bioprosthesis.