Purpose <p>Cannabis is commonly used among patients with cancer for palliative benefit. As the use of immune checkpoint inhibitors (ICIs) for cancer therapy increases, there is concern about potential interactions between ICIs and cannabis. Preclinical studies suggest that cannabis leads to immunosuppression, which could impair the function of ICIs. However, only a few clinical studies have investigated this relationship. The goal of this review is to synthesize reported immunomodulatory effects of cannabis in patients with and without cancer in order to better understand whether these preclinical findings translate to the clinical space.</p> Methods <p>A database search was conducted through Ovid Medline to identify relevant articles. Clinical studies investigating cannabis use in humans and the immune system were included. Preclinical studies and case studies were excluded. Information pertaining to immune changes with cannabis exposure was abstracted.</p> Results <p>Forty studies met inclusion criteria, including 9 randomized, placebo-controlled clinical trials. Analysis of immune-related markers demonstrated no change in cytokines, T-cell counts, and CRP in most studies with cannabis exposure. Among patients with autoimmune diseases, cannabis use showed improvements in clinical symptoms even while objective laboratory immune markers remained unchanged.</p> Conclusion <p>We did not find evidence of meaningful changes in immune parameters with cannabis use in the clinical setting across multiple diseases. In particular, immune markers relevant to ICI function did not appear to be associated with cannabis use. This evidence may provide some reassurance to patients and oncologists contemplating concomitant cannabis use with ICIs; however, additional well-controlled prospective studies are warranted in this setting.</p>