Chemomechanical preparation of the root canal includes both mechanical instrumentation and antibacterial irrigation, and is principally directed toward the elimination of micro-organisms from the root canal system. A variety of instruments and techniques have been developed and described for this critical stage of root canal treatment. Since their introduction in 1988, nickel-titanium (NiTi) rotary instruments have become a mainstay in clinical endodontics because of their exceptional ability to shape root canals with potentially fewer procedural complications. Safe clinical usage of NiTi instruments requires an understanding of basic metallurgy of the alloy including fracture mechanisms and their correlation to canal anatomy. This paper reviews the biologic principles of preparing root canals with an emphasis on correct use of current rotary NiTi instrumentation techniques and systems. The role and properties of contemporary root canal irrigants is also discussed.