Realist synthesis is a literature review methodology for understanding how, for whom, and under what circumstances complex interventions function in complex environments. Using a heuristic called the context-mechanism-outcome (CMO) configuration, realist synthesis produces evidence-informed theories about the interactions between intervention mechanisms and their implementation contexts. Public health interventions and their effects unfold over time and develop differently in different contexts. Much of what causes programs to function remains in a realm beyond empirical measurement. By scrutinizing the theories relevant to the interventions of interest, and by enhancing the conceptualization of complex outcomes, the realist approach deprioritizes evidence hierarchies and harnesses insights from diverse data sources to generate causal understanding. The dynamic learning process that can arise in conducting a realist synthesis may generate new ideas for program development and innovation apart from what can be achieved in reviews providing a summation and aggregation of quantified evidence.