Needleless connectors, used today as integral components of an infusion system, enhance healthcare worker safety. Currently, there are three design categories among needleless connectors: (1) split septum connectors, (2) luer activated valves and (3) luer valves with positive displacement. Numerous branded products are available within each category. Although needleless connectors offer enhanced safety features, there have been recurrent concerns about an increased risk of bacteremia associated with their use. However, until more evidence exists regarding the impact of mechanical design aspects on infection risk, none of the three currently available categories of needleless connectors can claim superiority.