Sickle cell disease is one of the 'grand' diseases in the terminology of Victorian pathology, because its widespread and multitudinous manifestations may affect any organ system in the body. It has served as a model of molecular disease being one of the first genetic disorders to be explainedat the molecular level. Since publication of the Second Edition, however, further advances have been made. Much has been learnt about the causes of variability in the natural history of the disease and of the reasons why there are such marked variations in the patterns of morbidity and mortality.As Director of The Jamaican Sickle Cell Unit, Graham Serjeant and his colleagues have shown the disease to be extremely variable ranging from a severe clinical course with death in early childhood to mildly affected patients living to the age of 80 years. This extreme variability within a singlegenotype implies that other factors, both genetic and environmental, must influence expression of the disease. This new edition contains many new references and incorporates the latest thinking on the biology of the disease and the best practice in its management.