This review gives an overview of the CB2 receptor (CB2R) knockout (CB2R-/-) mice phenotype and the work that has been carried out using this mutant mouse. Using the CB2R-/- mice, investigators have discovered the involvement of CB2R on immune cell function and development, infection, embryonic development, bone loss, liver disorders, pain, autoimmune inflammation, allergic dermatitis, atherosclerosis, apoptosis and chemotaxis. Using the CB2R-/- mice, investigators have also found that this receptor is not involved in cannabinoid-induced hypotension. In addition, the CB2R-/- mice have been used to determine specific tissue CB2R expression. The specificity of synthetic cannabinoid agonists, antagonists and anti-CB2R antibodies has been screened using tissues from CB2R-/- mice. Thus, the use of this mouse model has greatly helped reveal the diverse events involving the CB2R, and has aided in drug and antibody screening.