This article presents the state of the art of Lean principles applied in Emergency Departments through a systematic literature review. Our article extends previous work found in the literature to respond to the following questions: (i) What research problems in emergency departments can Lean principles help overcome? (ii) What Lean approaches and tools are used most often in this environment? (iii) What are the results and benefits obtained by these practices? and (iv) What research opportunities appear as gaps in the current state of the art on the subject? A six-step systematic review was performed following the guidance of the PRISMA method. The review analysis identified six main research problems where Lean was applied in Emergency Departments: (i) High Waiting Time and High Length of Hospital Stay; (ii) Health Safety; (iii) Process redesign; (iv) Management and Lessons Learned; (v) High Patient Flow; (vi) Cost Analysis. The six research problems’ main approaches identified were Lean Thinking, Multidisciplinary, Statistics, and Six Sigma. The leading Lean tools and methodologies were VSM, Teamwork, DMAIC, and Kaizen. The main benefits of applying Lean Principles were (a) reductions in waiting time, costs, length of hospital stay, patient flow, and procedure times; and (b) improvements in patient satisfaction, efficiency, productivity, standardization, relationships, safety, quality, and cost savings. Multidisciplinary integration of managers and work teams often yields good results. Finally, this study identifies knowledge gaps and new opportunities to study Lean best practices in healthcare organizations.