It can take years for a fraction of effective health care practices to reach patients who need them the most, potentially wasting millions of research dollar investments. This research-to-practice gap is attributed to lack of involvement of frontline health care clinicians and limited user-friendly tools to enable them to overcome barriers to uptake of effective practices in real-world settings, especially when faced with organizational constraints. The VA Quality Enhancement Research Initiative (QUERI) Roadmap for Implementation and Quality Improvement is a practical guide for clinicians and researchers to plan and deploy methods to support uptake of effective practices in routine care settings. The three phases of the QUERI Roadmap are Pre-implementation, Implementation, and Sustainment. Pre-implementation identifies high-priority needs, selects effective practices to address the needs, engages stakeholders to build implementation capacity, specifies practice adaptations and evaluation goals, and activates leadership support. Implementation focuses on involving clinical and research leaders to use implementation or quality improvement strategies that support, motivate, and inspire frontline clinicians to adopt and “own” the uptake of effective practices. Sustainment includes business case analyses and knowledge translation methods for practitioners to support ongoing implementation maintenance and improvement of effective practices over time. Integrating key literature and terminology, the QUERI Roadmap de-mystifies the application of implementation strategies and rigorous evaluation of these efforts to support practitioners and inform policy and population health improvements. Combining real-world experience with state-of-the art implementation and quality improvement science, the QUERI Roadmap ultimately makes implementation science usable and practical for investigators and practitioners alike.