A process change with the goal of decreasing and ultimately eliminating bloodstream infections associated with central catheters in critical care patients was implemented at Riverside Methodist Hospital. This process of implementation resulted in a culture change in the hospital’s medical surgical intensive care unit. Keys to success included a multidisciplinary team approach, support from persons with a stake in the process, and provision of continuous feedback. The lessons learned in this journey at Riverside Methodist Hospital can help caregivers at other hospitals decrease the occurrence of these life-threatening infections.