In this issue of JAMA Internal Medicine, Kravitz and colleagues1 report, to our knowledge, the largest randomized trial comparing n-of-1 randomized clinical trials (RCTs) applied in clinical care to standard care. The investigators enrolled 215 patients undergoing management for chronic musculoskeletal pain. The investigation is noteworthy for its innovative methodology, use of mobile health tools, and failure to demonstrate any important benefit of applying the n-of-1 methodology in clinical practice.