Over the decades, a wide array of nickel–titanium (NiTi) instruments has been introduced for shaping root canals. Each generation of instruments has had something new to offer and has been intended to improve upon previous generations. Many variables and physical properties influence the clinical performance of NiTi rotaries. Ultimately, clinical experience, handling properties, safety, and case outcomes should decide the fate of a particular instrument design. This review article summarizes the metallurgical and mechanical properties of NiTi endodontic instruments and the design features of each generation, with a special focus on the latest generation of NiTi instruments. Experimental and clinical evaluations of the performance of NiTi instruments in endodontic treatment are discussed.