Only a few studies have addressed the transport of 2-arachidonoylglycerol (2-AG), a naturally occurring agonist for cannabinoid receptors. Based upon saturation kinetics, these early reports have proposed that 2-AG enters the cell by a specific 2-AG transporter, via the putative anandamide transporter, or by simple diffusion. In this review, the uptake of 2-AG is discussed in light of the recent advances that have been made for anandamide transport, where the mechanism appears to be rate-limited diffusion through the membrane. Endocannabinoids may be a distinct class of agonists since they are hydrophobic and neutral, exhibiting similar biophysical properties to some anesthetics that freely diffuse through the membrane.