Background: Putting evidence into practice at the point of care delivery requires an understanding of implementation strategies that work, in what context and how. Objective: To identify methodological issues in implementation science using 4 studies as cases and make recommendations for further methods development. Research Design: Four cases are presented and methodological issues identified. For each issue raised, evidence on the state of the science is described. Results: Issues in implementation science identified include diverse conceptual frameworks, potential weaknesses in pragmatic study designs, and the paucity of standard concepts and measurement. Conclusions: Recommendations to advance methods in implementation include developing a core set of implementation concepts and metrics, generating standards for implementation methods including pragmatic trials, mixed methods designs, complex interventions and measurement, and endorsing reporting standards for implementation studies.