Criminology has paid increasing attention to the prospect that prevention programmes can cause harm. The Cambridge-Somerville Youth Study, a delinquency prevention experiment of 506 boys that began in 1939, provides some of the earliest evidence of programmatic iatrogenic effects. A series of hypotheses were advanced by Joan McCord and other scholars to explain these unintended effects. Drawing upon this scholarship, related research and developmental theory, this article examines the leading explanations and offers new appraisals of iatrogenic effects of crime prevention programmes. The research suggests that there is not a grand explanation, and we encourage a more nuanced perspective for understanding iatrogenic effects of crime prevention programmes. Implications for policy and practice are discussed.