Cattle show considerable variability in their responses to a wide range of disease challenges, and much of the variability is genetic. This review highlights genetic variation in disease susceptibility in Bos taurus cattle, with variation found at the breed level and also within breeds. Disease challenges come from bacteria and viruses, parasites and feed-borne toxins. For an animal to survive, it needs its own mechanisms for resisting these challenges, or for being resilient to them, or it must be protected artificially from them. Disease challenges have been classified as 'diseases from without', but there is also another class of genetic diseases resulting from inborn errors of metabolism, which might be called 'diseases from within'. Degrees of inheritance (heritabilities) are reviewed for a range of economically important traits including resistance to mastitis, ketosis, lameness, nematode parasites, external parasites, eye disease, respiratory disorders, tuberculosis, brucellosis, Johne's disease, foot-and-mouth disease, bovine spongiform encephalopathy, metabolic disorders caused by toxins found on the feed, and threshold levels of minerals and metabolites. Many, but not all, of the above require an immune response as part of the fight against an external challenge, and measurements have been made of general immune response as a way of describing or predicting how an animal will respond. There are now some examples of industry or breed societies applying selection for resistance to one or more diseases as part of a complete breeding objective in dairy cattle, beef cattle or dual purpose livestock. In most cases, industry and breed societies are in the early stages of applying effective selection pressure for resistance to specific cattle diseases, with the notable exceptions of Scandinavian cattle schemes, which lead the world in this respect.