Unanticipated Risk in Clinical Research ∗ ∗The editors have included Dr. Stephen Straus'original unedited contribution, penned for the book's 2002 edition and published with minor modification in the second edition in 2007, to honor his memory. This is a classic and compelling chapter with a story that remains relevant today. References to regulation and guidelines may not be current. The editors have added current references as of the time of publication to the end of the chapter.