Forty years of research and clinical practice have proved dopamine (DA) receptor antagonists to be effective agents in the treatment of Tourette's syndrome (TS), allowing a significant tic reduction of about 70%. Their main effect seems to be mediated by the blockade of the striatal DA-D2 receptors. Various typical and atypical agents are available and there is still discord between experts about which of them should be considered as first choice. In addition, there are suggestions to use DA receptor agonists such as pergolide or non-DA-modulating agents.The present chapter is focusing on the clinical pharmacology of DA-modulating agents in the treatment of TS. The introduction outlines their clinical relevance and touches on the hypotheses of the role of DA in the pathophysiology of TS. Subsequently, general information about the mechanisms of action and adverse effects are provided. The central part of the chapter forms a systematic review of all DA-modulating agents used in the treatment of TS, including an overview of studies on their effectiveness, and a critical discussion of their specific adverse effects. The present chapter closes with a summary of the body of evidence and a description of the resulting recommendations for the pharmacological treatment of TS.