A large segment of the proteome consists of disordered regions, yet in most cases, little is known about their mechanisms and functions. What are the roles of protein disorder in cell biology, and how do intrinsically disordered proteins function? These are the questions Cell’s Robert Kruger posed to Madan Babu, Julie Forman-Kay, and Richard Kriwacki. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.