Since 2002, evidence has been building that cannabinoids, including endocannabinoids and endocannabinoid‐like compounds, phytocannabinoids and synthetic cannabinoid ligands, bind to and activate the different isoforms of the nuclear receptors, peroxisome proliferator‐activated receptors (PPARs; α, β, and γ). This has been shown through the use of reporter gene assays, binding studies, the use of antagonists and knockout animals. Increasing use of tools to assess a potential role for PPAR activation in underpinning the physiological effects of cannabinoids means that a picture is emerging of the relevance of PPAR activation by cannabinoids. There is now evidence that activation of PPARα and γ mediate some of the anti‐inflammatory, analgesic, neuroprotective, and cardiovascular effects of cannabinoids, sometimes in combination with activation of the more traditional target sites of action such as CB1, CB2, and TRPV1. There is also a role for PPARα activation by cannabinoids in some of their central effects including memory acquisition, reward processing, food intake and body weight regulation. Activation of PPARγ plays a role in the apoptotic effects of cannabinoids. However, much further work is required to fully establish the profile of cannabinoid compounds at all isoforms of the PPAR family and the relevance of this in normal physiology and pathological situations. WIREs Membr Transp Signal 2013, 2:17–25. doi: 10.1002/wmts.73