Established tumors develop ways to elude destruction by the host immune system. Recent work has revealed that tumors can take advantage of the generation of metabolic dysregulation to inhibit immune responses. Effector T-cell functions are particularly sensitive to nutrient availability in the tumor microenvironment. In this review, we highlight experimental data supporting the importance of glucose, oxygen, tryptophan, and arginine for optimal T-cell function, and the mechanisms by which these nutrients may become depleted in the tumor microenvironment. These observations provide a conceptual framework for modulating metabolic features of the T cell-tumor interaction, toward the end of promoting more effective immune-mediated tumor destruction in vivo.