In this review, we have described the role of adenosine A2A receptor-driven interactions with other neurotransmitter systems, at multiple levels of psychopharmacology, from the molecular basis of receptor-receptor cross-talk, to pharmacological and genetic manipulations of A2AR activity, and the alteration of neuropsychiatric phenotypes in psychostimulant addiction, anxiety and depression, schizophrenia and learning and memory. The gene discussed is ADORA2A; the disease is schizophrenia.