Type 1 diabetes, rheumatoid arthritis, and Crohn disease seem clinically diverse, but they arise from acommon problem: poor discrimination between self and nonself. The search for specific markers identifying the cells underlying tolerance, and the genetic basis of their development and function promises much-needed new treatments for autoimmune diseases, which affect about one in twenty of the world's population.[1] A transcription factor called Foxp3 appears to be a prime player molecular basis of tolerance. This issue's Hot Papers documented how the molecular fox hunters found the first traces of their prey.[1-3]