Success in achieving the highest quality of patient care at lower cost depends significantly on effective management and continuous improvement of complex, interconnected and cross-functional processes. The root cause of most organizational, quality and safety problems can be found in the process. Effective process improvement framework integrates individual healthcare providers, teams, processes, methodologies, and information technology into a cohesive system while taking into account organizational culture, structure, strategy, existing resources, and overall capabilities. The key to the successful implementation of any process improvement framework is adaptation. There are many quality, safety and process improvement frameworks, methodologies, best practices, and standards available to organizations today. Depending on specific organizational needs and objectives, they all have certain advantages and disadvantages. There is no such thing as one-size-fits-all process improvement framework. Therefore, it is essential to adapt, integrate and appropriately contextualize Lean, Six Sigma, Human Factors Engineering, Plan-Do-Study-Act (PDSA) Cycle, Project Management, and any other complementary methodology for a specific organization. In the absence of clear process ownership and sustained leadership attention over a long period of time, most processes have tendency to become ineffective, inefficient, redundant, or simply inadequate to meet constantly changing needs and expectations. To increase the chances of achieving and sustaining operational excellence, continuous process improvement must become a way of life across the organization.