The present article provides a synthesis of the conceptual and statistical issues involved in using multisite randomized trials to learn about and from a distribution of heterogeneous program impacts across individuals and/or program sites. Learning "about" such a distribution involves estimating its mean value, detecting and quantifying its variation, and estimating site-specific impacts. Learning "from" such a distribution involves studying the factors that predict or explain impact variation. Part I of the article introduces the concepts and issues involved. Part II focuses on estimating the mean and variation of impacts of program "assignment." Part III extends the discussion to variation in the impacts of program "participation." Part IV considers how to use multisite trials to study "moderators" of program impacts (individual-level or site-level factors that influence these impacts) and "mediators" of program impacts (individual-level or site-level "mechanisms" that produce these impacts).