Natural (i.e. low-affinity, preimmune) IgM has a wide range of actions in the immune system. That IgM is important in defence against infection has been recognised for many years but recently, due to the generation of mouse models specifically deficient in serum IgM, other functions of serum IgM have been revealed. The participation of natural IgM in autoimmunity has been a subject of speculation for some time, but there is recent definitive evidence that demonstrates its protective role. This review focuses on these new areas of research, which also show that many pathologies not normally recognised as having an immunological basis are modulated by serum IgM.