Incremental approaches to introducing change in Canada's health systems have not sufficiently improved the quality of services and outcomes. Further progress requires 'large system transformation', considered to be the systematic effort to generate coordinated change across organisations sharing a common vision and goal. This essay draws on ongoing dialogue relating to transformation, and examines transformative efforts in the Saskatchewan health system. We aim to build a shared understanding of systems thinking in the context of transformation, and to outline examples of how systems thinking perspectives, with an emphasis on the role of evidence, may inform strategy for complex change initiatives.