This article reviews several common quality improvement methodologies, including the Model for Improvement, Lean, and Six Sigma. We demonstrate how these methods are based on a similar improvement science foundation. We describe the tools used to understand problems in the context of systems and the mechanisms to learn and build knowledge, using specific examples from the neonatology and pediatric literature. We conclude with a discussion on the importance of the human side of change in quality improvement, including team formation and culture.