These Guidelines for the Cleaning and Sterilization of Intraocular Surgical Instruments were written by the Ophthalmic Instrument Cleaning and Sterilization (OICS) Task Force, comprised of representatives of the American Society of Cataract and Refractive Surgery, the American Academy of Ophthalmology, and the Outpatient Ophthalmic Surgery Society. These consensus subspecialty guidelines include evidence-based recommendations regarding issues that may be unique to the cleaning and sterilization of intraocular instrumentation. A newly published OICS Task Force study supports the safety of common short-cycle instrument processing practices for sequential same-day anterior segment surgery. Other studies substantiate the risk of toxic anterior segment syndrome from routine use of enzymatic detergent, whose microscopic residues are difficult to eliminate from intraocular instrumentation. Finally, based on published international outcomes and endophthalmitis rates, future studies should critically evaluate a variety of operating room protocols that may increase cost, waste, and carbon footprint, without any actual safety benefit.