Policymakers globally are paying increasing attention to the challenges of providing more accessible and integrated mental health care. For transformative change to take place, thought needs to be given to the structure and form of evidence-informed change strategies at all levels: individual, organizational, community and complex, large systems. Yet few frameworks specifically consider the transfer of evidence-based programs across jurisdictions at regional and national levels; most are focused on local service implementation. This paper examines how a specific analytical model developed to assess and develop Knowledge Exchange (KE) can be applied to regional and national KE initiatives. It specifically examines the efforts of the International Knowledge Exchange Network for Mental Health (IKEN-MH), and the associated community of interest on change and improvement, to support mental health systems change at these levels. Using a theoretical model, the Promoting Action on Research Implementation in Health Services framework (Kitson, Harvey, & McCormack, 1998, Rycroft-Malone, et al., 2002), we explore systems change efforts according to the constructs of evidence, context and facilitation. By matching some exemplars in the use of KE for mental health best practice against this model, the potential strategies of the IKEN-MH to assist transformational change emerge.