The repeated administration of cocaine produces enduring neuroadaptations that are associated with enhanced behavioral responsiveness to cocaine administration and lead to cocaine addiction and the manifestation of paranoid psychosis. This review describes the effect of chronic cocaine administration on dopamine and glutamate transmission in the nucleus accumbens, and discusses the relevance of these changes in the initiation of drug craving and relapse to drug abuse. Recent findings suggest that glutamate transmission in the nucleus accumbens is a dominant precipitator of relapse to drug-seeking activity, whereas both dopamine and glutamate transmission are important for sustaining drug-taking behavior.