Quality improvement (QI) and comparative effectiveness research (CER) are increasingly important areas of study for the pediatric hospitalist. The focus of this article is to provide the relevant background, definitions, framework, infrastructure, and resources needed to both inform and engage the pediatric hospital medicine (PHM) community on QI and CER. In mastering these activities, PHM physicians will have a key role in shaping the health care transformation expected over the next decade and beyond.