Context.-Cancer immunotherapy provides unprecedented rates of durable clinical benefit to late-stage cancer patients across many tumor types, but there remains a critical need for biomarkers to accurately predict clinical response. Although some cancer immunotherapy tests are associated with approved therapies and considered validated, other biomarkers are still emerging and at various states of clinical and translational exploration. Objective.-To provide pathologists with a current and practical update on the evolving field of cancer immunotherapy testing. The scientific background, clinical data, and testing methodology for the following cancer immunotherapy biomarkers are reviewed: programmed death ligand-1 (PD-L1), mismatch repair, microsatellite instability, tumor mutational burden, polymerase d and e mutations, cancer neoantigens, tumor-infiltrating lymphocytes, transcriptional signatures of immune responsiveness, cancer immunotherapy resistance biomarkers, and the microbiome. Data Sources.-Selected scientific publications and clinical trial data representing the current field of cancer immunotherapy. Conclusions.-The cancer immunotherapy field, including the use of biomarker testing to predict patient response, is still in evolution. PD-L1, mismatch repair, and microsatellite instability testing are helping to guide the use of US Food and Drug Administration-approved therapies, but there remains a need for better predictors of response and resistance. Several categories of tumor and patient characteristics underlying immune responsiveness are emerging and may represent the next generation of cancer immunotherapy predictive biomarkers. Pathologists have important roles and responsibilities as the field of cancer immunotherapy continues to develop, including leadership of translational studies, exploration of novel biomarkers, and the accurate and timely implementation of newly approved and validated companion diagnostics.