In multiple malignancies, checkpoint inhibitor therapy has an established role in the first-line treatment setting. However, only a subset of patients benefit from checkpoint inhibition, and as a result, the field of biomarker research is active. Molecular imaging with the use of positron emission tomography (PET) is one of the biomarkers that is being studied. PET tracers such as conventional 18F-FDG but also PD-(L)1 directed tracers are being evaluated for their predictive power. Furthermore, the use of artificial intelligence is under evaluation for the purpose of response prediction. Response evaluation during checkpoint inhibitor therapy can be challenging due to the different response patterns that can be observed compared to traditional chemotherapy. The additional information provided by PET can potentially be of value to evaluate a response early after the start of treatment and provide the clinician with important information about the efficacy of immunotherapy. Furthermore, the use of PET to stratify between patients with a complete response and those with a residual disease can potentially guide clinicians to identify patients for which immunotherapy can be discontinued and patients for whom the treatment needs to be escalated. This review provides an overview of the use of positron emission tomography (PET) to predict and evaluate treatment response to immunotherapy.