Attention to the improvement of safety in healthcare lately has focused on healthcare-associated infections, including many that occur in the intensive care unit, such as catheter-related bloodstream infections and ventilator-associated pneumonias. Great strides have been made in decreasing the rates of intensive care unit hospital-acquired infections in the past decade. This is attributable to a number of factors, including standardization of care, technological advances, provider payment reform, and consumer activism. Teamwork and communication remain the most important facets in patient safety. The papers in this supplement examine the roles of human factors and process engineering, survey a spectrum of infection control and safety challenges encountered by critical care practitioners, and assess the future challenges for continued improvement in our systems of care.