Traditionally, immunotherapy agent selection and treatment strategies are guided by biopsy-based histological information. However, biopsies are limited in that they are invasive, provide static information regarding the tumor immune microenvironment, and only sample a small part of one tumor site. The tumor microenvironment is dynamic and heterogenous. As a result, the immune milieu at one site may be distinct from other metastatic sites. These factors make identifying which patients are likely to respond to different immunotherapies and which harbor intrinsic resistance mechanisms difficult to identify based on a biopsy alone. As such, there is significant interest in alternative methodologies that better characterize the tumor immune microenvironment and monitor immunotherapy response. PET imaging potentially offers a non-invasive way to characterize the tumor immune microenvironment at the primary tumor and metastases and allow for longitudinal characterization. Herein, we review pre-clinically and clinically tested T cell-targeted PET radiopharmaceuticals, as T cells have been the dominant immunotherapy target, and their utility in both evaluating response to immunotherapy and in understanding the systemic immune response to treatment with immunotherapeutics.