With the increasing number of people suffering from heart valve diseases (e.g., stenosis and/or insufficiency), the attention paid to prosthetic heart valves has grown significantly. Developing a prosthetic device that fully replaces the functionality of the native valve remains a huge challenge. Polymeric heart valves (PHVs) represent an appealing option, offering the potential to combine the robustness of mechanical valves with the enhanced biocompatibility of bioprosthetic ones. Over the years, novel biomaterials (such as promising new polymers and nanocomposites) and innovative designs have been explored for possible applications in manufacturing PHVs. This work provides a comprehensive overview of PHVs’ evolution in terms of materials, design, and fabrication techniques, including in vitro and in vivo studies. Moreover, it addresses the drawbacks associated with PHV implementation, such as their limited biocompatibility and propensity for sudden failure in vivo. Future directions for further development are presented. Notably, PHVs can be particularly relevant for transcatheter application, the most recent minimally invasive approach for heart valve replacement. Despite current challenges, PHVs represent a promising area of research with the potential to revolutionize the treatment of heart valve diseases, offering more durable and less invasive solutions for patients.