Since its food and drug administration (FDA) approval in 2011, transcatheter aortic valve replacement (TAVR) has revolutionized the highly prevalent disease of aortic stenosis. In this review, we present a comprehensive overview of the data and considerations for utilization of TAVR in special populations who were either excluded from or not adequately represented in the seminal TAVR trials, due to high-risk valvular and/or systemic factors. These include nonagenarians, patients with renal dysfunction, chronic thrombocytopenia, bicuspid aortic valve, rheumatic valve disease, patients with failed aortic valve bioprosthesis requiring valve-in-valve intervention and patients with mixed aortic valve disease. In short, TAVR is a feasible therapeutic strategy in high-risk and special populations with mortality benefit and improvement in quality of life. Randomized controlled trials in high-risk populations are recommended to confirm results from observational studies.