This review describes physiological aspects of CB1 receptors, pharmacological roles of ECs and the EC-degrading enzyme fatty acid amid hydrolase (FAAH), functional crosstalk between ECs and TRPV1, the interaction between ECs and the sympathetic nervous system in RA, the influence of ECs on arthritis disease sequelae in mice and humans, and direct immunomodulatory effects of CB1 signaling in the periphery and in the brain. The gene discussed is CNR1; the disease is rheumatoid arthritis.