The immunological process of clonal selection requires a rapid burst in lymphocyte proliferation, and this involves a metabolic shift to provide energy and the building blocks of new cells. After activation, naive and memory T cells switch from the oxidation of free fatty acids to glycolysis and glutaminolysis to meet these demands. Beyond this, however, the availability of specific metabolites and the pathways that process them interconnect with signaling events in the cell to influence cell cycle, differentiation, cell death and immunological function. Here we define 'metabolic checkpoints' that represent such interconnections and provide examples of how these checkpoints sense metabolic status and transduce signals to affect T lymphocyte responses.