Immune responses can lead to treatment success in cancer patients. Tumor antigen-specific T cells play leading roles, and a large number of additional biological mechanisms can influence the clinical outcome. Monitoring immune responses in cancer patients provides information on disease-induced immune properties (baseline), and on treatment efficacy. In this chapter we outline the current status of immune monitoring assays. They must be critically evaluated and optimized, with the aim to selectively focus on those approaches that provide in vivo relevant results, paving the way to selectively apply meaningful assays and to identify prognostic and predictive biomarkers that support clinical care.