Since the 1990s, ‘personalized medicine’ has become a powerful language in which to imagine significant change in medicine from a ‘one size fits all’ model to one that tailors prediction, diagnosis and treatment to the individual. Two decades on, personalized medicine remains a contested vision of the future. Drawing on work in the sociology of expectations, I argue that expectations about genomics to bring about a personalized medicine are ‘prefigured’ by other ways in which knowledge about individual specificity and variability have been at the centre of claims and counterclaims about the future of medicine since the 19th century. Examining how and why medical universalism or a ‘one size fits all’ model of medicine has been contested over time, I conclude by considering the limits of what genomics has to offer for personalizing medicine.