Indications for the use of immunotherapy in oncology are increasing rapidly. Each classification of immunotherapy has its own unique characteristics. Understanding the mechanism of action and the potential for infusion reactions will help advanced practice providers (APPs) to prepare patients and clinical staff for expected outcomes. Timely identification, grading, and documentation of each infusion reaction can decrease cost and patient length of stay and improve patient outcomes. The National Cancer Institute’s Common Terminology Criteria for Adverse Events provides grading criteria guidelines for APPs to rechallenge patients.