Cytokines have crucial functions in the development, differentiation and regulation of immune cells. As a result, dysregulation of cytokine production or action is thought to have a central role in the development of autoimmunity and autoimmune disease. Some cytokines, such as interleukin-2, tumour-necrosis factor and interferons—ostensibly, the'bad guys' in terms of disease pathogenesis—are well known for the promotion of immune and inflammatory responses. However, these cytokines also have crucial immunosuppressive functions and so, paradoxically, can also be'good guys'. The balance between the pro-inflammatory and immunosuppressive functions of these well-known cytokines and the implications for the pathogenesis of autoimmune disease is the focus of this review.