Cannabis includes 140 active cannabinoid compounds, the most important of which are tetrahydrocannabinol and cannabidiol (CBD). Tetrahydrocannabinol is primarily responsible for the intoxicating effects of cannabis; CBD has potential therapeutic effects, including reduction in chronic pain. Recent legislative changes have resulted in the legal availability of cannabinoids in all 50 states, as well as a marked increase in patients’ interest in their use. Despite an abundance of data, albeit of varied quality, clinicians may feel poorly prepared to counsel patients seeking advice on the suitability of CBD products for various indications, particularly chronic neuropathic pain. In 2018, on the basis of a systematic review of the literature, a Canadian Evidence Review Group published a guideline with recommendations for clinicians on prescribing cannabinoids in primary care practice. The overall quality of evidence was low to very low. In a meta-analysis of 15 randomized trials of medical cannabis for treating chronic pain, 39% of patients achieved at least a 30% reduction in pain. The corresponding value for placebo-treated patients was 30%; the number needed to treat was 11. More evidence exists for neuropathic pain than for other types of noncancer pain. Here, a general internist with a focus on addiction medicine and an addiction psychiatrist discuss how they would apply the literature to make recommendations for a patient with painful diabetic neuropathy, including counseling on both potential benefits and harms.