Addiction leads to substantial human suffering as well as to tremendous economical costs for our society. A secret to the understanding of this pathology lies in unraveling the function of a specific brain region named nucleus accumbens (NAc). The NAc regulates several behavioral outputs that are affected in addiction, including motor control, learning of habits, motivational and reward-related learning. To communicate with each other, brain cells, neurons, use a combination of electrical and secreted chemical signals, called neurotransmitters. Amongst these brain neurotransmitters, dopamine, acetylcholine, GABA and glutamate are key players in the NAc. Dysfunction of communication in the NAc underlies the development of drug dependence. For instance, dopamine transmission in the NAc is critical for reward prediction as well as addiction to drugs such as cocaine, morphine, nicotine amphetamine and alcohol. Acetylcholine-secreting neurons (known as TANs) also regulate many of the pathological alterations in addiction. We have recently made the astonishing discovery that acetylcholine-secreting neurons can release the neurotransmitter glutamate in addition to acetylcholine. This finding suggests that these neurons can communicate with other cells in the NAc using two different chemical codes. Hence, by using these two separate “languages” TANs can provide distinct forms of information to other neurons in the NAc. We have recently uncovered evidence that it is glutamate release, and not acetylcholine release, by these “bilingual” neurons that is critical in mediating drug–induced effect. Furthermore, we have identified individuals suffering from severe addictions, who carry mutations in the machinery allowing glutamate release from TANs. The ultimate goal of our current proposal is to decipher how TANs, by sending these two chemical codes, can regulate the NAc in healthy and diseased states. Understanding this “neuronal bilingualism” will lead to the refinement of screening strategies and medications for the treatment of NAc-related diseases.