Cannabis has garnered increased interest for its application in treating a variety of medical ailments and has been approved by the Food and Drug Administration (FDA) for chemotherapy-induced nausea and acquired immunodeficiency syndrome (AIDS)-associated weight loss. The potential utility of cannabis in the treatment of chronic pain is an emerging and controversial field. Randomized controlled trials evaluating the efficacy of cannabinoid therapy have shown positive outcomes in chronic neuropathic and oncologic pain. This chapter covers the consideration of cannabis and mechanism of action, determining risks, mechanism of action and administration of cannabis, and safety monitoring and adverse effects.