Methods to identify disease risk factors from a series of cases are considered. These include methods that compare risk factor levels among diagnostic categories and methods that relate risk factor levels to age at diagnosis, with a single diagnostic category. Statistical aspects considered include modelling assumptions, parameter identifiability, hypothesis-testing efficiency, assumptions concerning unsampled diagnostic categories and requirements for risk factor data and confounding factor data. It is argued that methods to identify risk factors using data on a single diagnostic category involve such strong assumptions that they have limited usefulness. Analyses that compare risk factor levels among diagnostic categories, on the other hand, should continue to play an important role in epidemiologic research, though there are important limitations in relation to analyses involving disease-free controls.