Many of the most striking traits we recognise in cattle are caused by one or a small number of large effect mutations. These include breed-defining characteristics such as coat colours and patterns, hair length, and horn status. Many deleterious effects in cattle can also be attributed to single genes, with phenotypic impacts ranging from mild (e.g. crop ears), to severe (embryonic lethality). This chapter will summarise a range of traits impacted by major effect genes in cattle, discussing examples of mutation discoveries with a focus on the methods used to identify these effects. The review includes analysis of emerging technologies and methods being applied to mutation discovery in cattle, examining how new molecular innovations and large-scale genomic data are playing increasingly important roles in causal gene and mutation identification.