A key feature of human and animal behavior is the ability to learn from environmental stimuli to adapt efficiently. Under physiological conditions, dopaminergic (DA) neurons are used to evaluate and learn new sensory information and adjust their behaviors to maximize rewards and minimize aversive consequences. The two main DA pathways in the mesencephalon originate from the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Both in vivo and in vitro studies have established that DA neurons exhibit spontaneous spike firing that is driven by intrinsic electrophysiological properties, with their activity modulated by afferent inputs and a number of neuromodulators, including endocannabinoids. In the VTA and SNpc, cannabinoid type 1 (CB1) and ionotropic transient receptor potential vanilloid type 1 (TRPV1) receptors, as well as their endogenous ligands, mainly anandamide and 2-arachidonoylglycerol, are abundantly expressed. This chapter attempts to summarize some of the major research findings demonstrating that SNpc and VTA DA neurons vary significantly in their molecular and physiological properties according to target location and that endocannabinoids act on GABAergic, glutamatergic, and cholinergic terminals to participate in discrete mechanisms aimed at DA cell homeostatic regulation. As a result, given the role of the endocannabinoid system in modulating DA neuronal function of the SNpc and the VTA, they might take part in associative learning, reward signaling, goal-directed behavior, motor skill learning, and action-habit transformation. These considerations help explain the correlation between an unbalanced endocannabinoid signal and altered DA-dependent processes underpinning the diverse pathological conditions of both the nigrostriatal and mesocorticolimbic systems.