In healthy individuals, metabolically quiescent T cells survey lymph nodes and peripheral tissues in search of cognate antigens. During infection, T cells that encounter cognate antigens are activated and — in a context-specific manner — proliferate and/or differentiate to become effector T cells. This process is accompanied by important changes in cellular metabolism (known as metabolic reprogramming). The magnitude and spectrum of metabolic reprogramming as it occurs in T cells in the context of acute infection ensure host survival. By contrast, altered T cell metabolism, and hence function, is also observed in various disease states, in which T cells actively contribute to pathology. In this Review, we introduce the idea that the spectrum of immune cell metabolic states can provide a basis for categorizing human diseases. Specifically, we first summarize the metabolic and interlinked signalling requirements of T cells responding to acute infection. We then discuss how metabolic reprogramming of T cells is linked to disease.