The adaptive immune response plays a critical role in detecting, eliminating, and creating a memory toward foreign pathogens and malignant cells. Demonstration of the specific and effective target killing of T cells in cancer has reignited interest in the study and therapeutic manipulation of the interaction between tumor and immune system. To both improve therapeutic efficacy and reduce adverse events, accurate monitoring of the activation of T cells is required. Several approaches to monitoring not just the presence, but importantly the activation, of T cells have been developed. Here, we review the recent advances in T-cell activation imaging and future directions for potential implementation into clinical utility.