This case study outlines key considerations for healthcare organizations experiencing significant transformational change, based on the experience of Ontario Shores Centre for Mental Health Sciences (Ontario Shores), formerly Whitby Mental Health Centre. Significant systemic change requires specific and intentional efforts from the leaders tasked with carrying out transformational activities. This article presents the perspectives of leaders involved in the transformation of Ontario Shores as it moved from a government-based agency to a stand-alone specialty psychiatric hospital in 2006. During this time, several conventional strategies were employed to manage the transition, but various critical approaches also emerged that assisted the organization to effect significant change and achieve marked improvements over key evaluation metrics. These critical strategies included maximizing the distinct and collective roles of governance and leadership; balancing strategy and action through a culture of accountability; leveraging strategic communication opportunities; and shifting the organizational mindset.