Metabolic programming is emerging as a critical mechanism to alter immune cell activation, differentiation and function. Targeting metabolism does not completely suppress or activate the immune system but selectively regulates immune responses. The different metabolic requirements of the diverse cells that constitute an immune response provide a unique opportunity to separate effector functions from regulatory functions. Likewise, cells can be metabolically reprogrammed to promote either their short-term effector functions or long-term memory capacity. Studies in the growing field of immunometabolism support a paradigm of ‘cellular selectivity based on demand’, in which generic inhibitors of ubiquitous metabolic processes selectively affect cells with the greatest metabolic demand and have few effects on other cells of the body. Targeting metabolism, rather than particular cell types or cytokines, in metabolically demanding processes such as autoimmunity, graft rejection, cancer and uncontrolled inflammation could lead to successful strategies in controlling the pathogenesis of these complex disorders.