Preliminary data presented at conferences and in the patent literature introduced the possibility the orphan receptor GPR55 might account for some of the well-documented non-CB(1), non-CB(2) effects reported for certain cannabinoid ligands. Several peer-reviewed publications have recently emerged in which the pharmacology of the cannabinoids at GPR55 has been probed in more depth. Despite this, the classification of GPR55 as a cannabinoid receptor remains a contentious issue. The weight of evidence points to GPR55 as a receptor that is activated by certain cannabinoid ligands and by the bioactive lipid l-alpha-lysophosphatidylinsoitol. It couples to G(12) proteins, activates RhoA and mobilizes intracellular Ca(2+), possibly in an agonist- and tissue-dependant manner, thus displaying 'agonist functional selectivity'. Here, I review the recent literature in an effort to glean the key controversies and outstanding questions surrounding the interaction between cannabinoids and this orphan receptor.