Framework synthesis is one systematic review method employed to address health care practice and policy. Adapted from framework analysis methods, it has been used increasingly, using both qualitative and mixed-method systematic review methods. This article demonstrates a spectrum of approaches to framework synthesis that are dependent on the extent to which theory is tentative, emergent, refined, or established; and that stakeholder involvement may help to understand the topic's complexity where theory is more nascent. The choice of approach depends on the degree of match with existing theories and, in the absence of existing theory, the scale and heterogeneity of the literature to be managed.