Medication errors in intensive care units put patients at risk for injury or death every day. Safety requires an organized and systematic approach to improving the tasks, technology, environment, and organizational culture associated with medication systems. The Systems Engineering Initiative for Patient Safety model can help leaders and health care providers understand the complicated and high-risk work associated with critical care. Using this model, the author combines a human factors approach with the well-known structure-process-outcome model of quality improvement to examine research literature. The literature review reveals that human factors, including stress, high workloads, knowledge deficits, and performance deficits, are associated with medication errors. Factors contributing to medication errors are frequent interruptions, communication problems, and poor fit of health information technology to the workflow of providers. Multifaceted medication safety interventions are needed so that human factors and system problems can be addressed simultaneously.