This article reviews stimuli-responsive and biostable polyurethanes (PUs) and discusses biomedical applications of smart PUs with a particular focus on long-term implantable PU biomaterials such as PU generated artificial blood vessels, artificial intervertebral discs (IVDs), and intravaginal rings (IVRs). Recently, smart PUs have been actively researched to enhance bioactivity, biocompatibility, and reduce drug side effects. Although biodegradability is important in regenerative medicine, biostability of PU plays a key role for long-term implantable biomaterials. This article reviews recent publications of research and inventions of stimuli-responsive and biostable PUs. Applications of smart PUs in long-term implantable biomaterials are discussed and linked to the future outlook of smart biostable PU biomaterials.