Instrument reprocessing has an interesting history. Prior to guidelines from federal, accrediting and professional agencies, cleaning processes were often determined by a member of leadership and what they thought would work best. Manufacturers are now required to provide information needed by processing personnel to reach recommended or required sterilization parameters. Each medical device comes with manufacturer instructions for use (IFU), also known as manufacturer’s instructions, and they should be readily accessible to all end users. Advances in medical technology have led to more complex instrument design, which in turn has led to more complicated IFUs. Healthcare organizations must put processes in place that help take the mystery out of the IFUs, provide effective training, empower personnel to identify areas of noncompliance and, most importantly, require compliance to help break the chain of infection and provide safe patient care.