Glycine plays a key role in regulating inhibitory neurotransmission in the spinal cord and concentrations of glycine in the CNS are regulated by two subtypes of high affinity glycine transporters, GlyT1 and GlyT2. In this mini review we will discuss a series of lipid inhibitors of GlyT2 that show promise as analgesics in the treatment of neuropathic and inflammatory pain. N-arachidonyl-glycine inhibits the rate of transport by GlyT2, but has very little or no activity on GlyT1. We will discuss structure–activity studies of the actions of related lipids on GlyT2 and also the characterization of a more potent lipid inhibitor of GlyT2, oleoyl-l-carnitine. Both N-arachidonyl-glycine and oleoyl-l-carnitine show specificity for GlyT2 over GlyT1, which has allowed the use of chimeric GlyT1/GlyT2 transporters to begin characterizing the molecular basis for specificity and mechanism of action of these lipid inhibitors. Although our understanding of the molecular basis for lipid inhibition is still in its infancy, it appears that extracellular loop 4 of GlyT2 plays an important role in the inhibitory mechanism.