ICRP Publication 83 reviews data on naturally occurring multifactorial diseases and develops a mathematical model to predict the impact of radiation induced mutations on the frequencies of these diseases in the population. It provides a broad outline of the aetiological features and examples of multifactorial diseases. It considers the concepts and models used to explain their inheritance patterns, with particular emphasis on the Multifactorial Threshold Model. Conceptual differences from ‘mendelian’ diseases are discussed, and pertinent epidemiology is reviewed. Particular attention is paid to diabetes mellitus and to coronary heart disease. Mechanistic models in population genetics are considered. The concepts of liability, threshold, mutation-selection balance, and mutation component are integrated into a Finite Locus Threshold Model as a basis for risk estimation. The relevance of these findings for estimation of radiation risk of multifactorial diseases is discussed.