The last 4 decades have seen an evolution in the application of cementless technology for the biological fixation of implants in total knee arthroplasty (TKA). Although first generation systems demonstrated variability in performance with many early failures because of aseptic loosening, advances in material science, tribology, and improved knowledge of knee kinematics has since allowed contemporary primary cementless total knee systems to perform at levels that approach or exceed that associated with cemented fixation. Published series at 10 to 20 years follow-up have demonstrated primary cementless TKA survival of contemporary designs that is comparable with or exceeds that of its cemented counterpart, with some series demonstrating no revisions for aseptic loosening. A higher degree of precision and accuracy in bone preparation and soft tissue balancing seems to be required when utilizing biologically fixed implants. Although originally explored to address the higher demands of the physiologically younger, more active population of patients, cementless technology offers potential benefits in bone conservation, simplifying the performance of the TKA procedure and in increasing operating room efficiency. In addition, theoretical potential reductions in perioperative morbidity and mortality may be realized in association with a shorter duration surgery. Continuing advances in the areas of material science, additive manufacturing, and system design simplification portend a continued positive and expanding role for cementless fixation in both primary and revision TKA in the near and distant future.