Basophils are the rarest granulocytes and represent less than 1% of peripheral blood leukocytes. They are evolutionarily conserved in many animal species, but their functional significance remained an enigma long after their discovery by Paul Ehrlich in 1879. Studies of basophils were hindered by their rarity, by difficulties in identifying them, and by the paucity of useful analytical tools. Because basophils display several characteristics shared by tissue-resident mast cells, they were often considered minor and possibly redundant relatives of mast cells or even blood-circulating precursors of mast cells. However, newly developed tools for their functional analysis, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have fueled basophil research and defined previously unrecognized functions of basophils. We now appreciate that basophils play nonredundant roles in acquired immunity regulation, protective immunity to pathogens, and immunological disorders such as allergy and autoimmunity.