The endocannabinoids are signaling lipids present in many living organisms. They activate G protein-coupled cannabinoid receptors to modulate a broad range of biological processes that include emotion, cognition, inflammation and reproduction. The endocannabinoids are embedded in an interconnected network of cellular lipid pathways, the regulation of which is likely to control the strength and duration of endocannabinoid signals. Therefore, physiopathological or pharmacological perturbations of these pathways may indirectly affect endocannabinoid activity and, vice versa, endocannabinoid activity may influence lipid pathways involved in other metabolic and signaling events. Recent progress in liquid chromatography and mass spectrometry has fueled the development of targeted lipidomic approaches, which allow researchers to examine complex lipid interactions in cells and gain a broader view of the endocannabinoid system. Here, we review these new developments from the perspective of our laboratory's experience in the field.