Preclinical and clinical studies have sought to better understand the effect of anesthetic agents, both volatile and intravenous, and perioperative adjuvant medications on immune function. The immune system has evolved to incorporate both innate and adaptive components, which are delicately interwoven and essential for host defense from pathogens and malignancy. This review summarizes the complex and nuanced relationship that exists between each anesthetic agent or perioperative adjuvant medication studied and innate and adaptive immune function with resultant clinical implications. The most commonly used anesthetic agents were chosen for review including volatile agents (sevoflurane, isoflurane, desflurane, and halothane), intravenous agents (propofol, ketamine, etomidate, and dexmedetomidine), and perioperative adjuvant medications (benzodiazepines, opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and local anesthetic agents). Patients who undergo surgery experience varying combinations of the aforementioned anesthetic agents and adjuncts, depending on the type of surgery and their comorbidities. Each has unique effects on immunity, which may be more or less ideal depending on the clinical situation. Further study is needed to better understand the clinical effects of these relationships so that patient-specific strategies can be developed to improve surgical outcomes.