In Reply The letters from Vohra and Punja and Smith about our recent Original Investigation1 underscore the same crucial point: patients may vary not only in their response to treatment, but also in their response to n-of-1 trials. Vohra and Punja offer an ardent counterpoint to Mirza and Guyatt’s conclusion that n-of-1 trials are a “beautiful idea being vanquished by cruel and ugly evidence.”2(1379) Smith’s story offers an inspiring example of how n-of-1 trials may be applied informally in the service of better, more patient-centered care.