Life is a nonequilibrium phenomenon: Metabolism provides a continuous supply of energy that drives nearly all cellular processes. However, very little is known about how much energy different cellular processes use, i.e., their energetic costs. The most direct experimental measurements of these costs involve modulating the activity of cellular processes and determining the resulting changes in energetic fluxes. In this review, we present a flux balance framework to aid in the design and interpretation of such experiments and discuss the challenges associated with measuring the relevant metabolic fluxes. We then describe selected techniques that enable measurement of these fluxes. Finally, we review prior experimental and theoretical work that has employed techniques from biochemistry and nonequilibrium physics to determine the energetic costs of cellular processes.