The use of immunotherapy in the treatment of cancer has resulted in a paradigm shift in clinical outcomes and in the correlative biomarkers that are most useful to evaluate in cancer patients. While several immunotherapeutic approaches have shown great promise, and several checkpoint inhibitors have been approved in the first and second line setting for multiple cancer types, major challenges remain in identifying the population of patients most likely to respond and in accurately monitoring clinical response while patients are receiving treatment. To best evaluate these prognostic and correlative parameters, the relationship between the anti-tumor immune response and treatment response should be evaluated. Sensitive and specific immune assays, therefore, need to be employed in patients receiving immunotherapy treatment. This review explores some of the current immunotherapies being assessed in cancer patients and describes the experimental tools available for monitoring the anti-tumor response prior to treatment or in patients receiving treatment. Studies of the correlation between these responses, as determined by these experimental assays, and response to immunotherapy should be performed to better select patients who will likely benefit from the different available immunotherapeutic treatments, to select the appropriate treatment approach, and to carefully monitor the response while on therapy.