While cannabis has remained federally illegal in the United States since the passage of the Marijuana Tax Act of 1937, The US Patent and Trademark Office has been issuing cannabis-related patents since 1942. The U.S. Department of Health and Human Services patented (US Patent No. 6,630,507) some of the basic work on the medical potential of cannabinoids in 2003. While the government’s view of cannabis has had no apparent dampening effect on patent activity per se, it remains likely that the opening of markets by the progressive legalization of cannabis and its resultant entry into mainstream medical practice will stimulate new levels of activity.Since 1942, nearly 1,500 cannabis-related patent applications have been filed in the US with the vast majority having been filed in the previous 25 years. Approximately half of these applications have been issued as patents and some have already expired, leaving ~500 currently enforceable patents and ~300 pending applications. U.S. patent references can be divided into three large and partially overlapping categories: (1) cannabis compositions, drug formulations, and methods of preparation, (2) characterization of cannabis compounds in terms of how they engage with human endocannabinoid receptors, and (3) methods of treating diseases with cannabinoids.Entities that have filed cannabis patents can also be divided into three categories: (1) large pharmaceutical companies, (2) universities and research institutes, and (3) small and midsize companies. The patent filing activity of the first and second categories peaked in 2006–2007 and has declined steadily since then. Small and midsize companies, however, are now very active in filing patents and account for nearly all current cannabis patent filing activity. It is notable that, to date, no cannabis-related patent applications have surfaced from big American food companies, agricultural companies, or tobacco companies.The decline in patent filing by big pharma may seem surprising without historical context. It was only in the 1970’s that the role of hormone and neurotransmitter receptors in the mechanism of drug action began to be appreciated by academic and pharmaceutical researchers. This has since become a critical aspect of understanding the physiology of any drug under development. When discovered in the 1990s that cannabinoid compounds interacted with the endocannabinoid receptors present in human cells, pharmaceutical and academic discovery machines were alert and in high gear. The industrial and academic cohorts, with their vast expertise in chemistry, quickly figured out the main cannabinoid compounds, their synthetic pathways, and extraction methodologies.Thus, a wave of cannabis innovation within research institutes and pharmaceutical labs crested in 2006-2007 and has been subsiding ever since; a common pattern as a layer of knowledge is built. It would be myopic and misinformed to interpret the current nadir in patent activity on the part of pharmaceutical players as a lack of interest in the cannabis space.Small and medium size companies innovating in the cannabis space are building on and expanding territory opened up by big pharma and universities. Smaller companies are now focusing on aspects of composition and formulation along with treatment of specific diseases. Additionally, small companies are opening up new niches such as (1) distinctive cannabinoid and terpene profiles and formulations with more efficient biological availability for use in beverages, foods, and medicine, and (2) industrial scale fermentation approaches to production (i.e., non plant-based) that can potentially deliver specific, quality-assured active agent profiles.Patenting cannabis plants themselves is another area of patent activity that has attracted attention and may represent commercial opportunity. Plants can be patented in two ways; by way of “utility patents” (~95% of all patents) or by way of a separate “plant patent” category. Plant patents are narrowly focused on a single “parent” plant and its direct descendants; this category of patents is primarily directed to flowers and food crops. Plant-directed utility patents are not limited to direct plant descendants and can cover any cannabis plant that meets the criteria defined by the patent claims. Utility patents thus have a broader scope than plant patents and are therefore considered to have greater commercial value.Truly innovative developments in cannabis can become intellectual property if captured in patent applications. If the patent owner prevails during patent prosecution and emerges with an issued patent, it becomes a commercial asset that can be used in licensing transactions or as an instrument that can be asserted in a lawsuit against an accused infringing competitor. A risk inherent in suing an accused infringer is that the validity of the asserted patent claims can be challenged by the defendant in court based on prior art or other grounds. To date, we have seen no infringement lawsuits in the cannabis space. Those who astutely and persistently pursue patents are playing a long game whose outcome is rarely clear at the onset but which can ultimately play an important role in a competitive market.