Adenosine A(2A) receptors are highly concentrated in the striatum, where they play an important modulatory role of glutamatergic transmission to the GABAergic enkephalinergic neuron, which function is particularly compromised in Parkinson's disease and in the early stages of Huntington's disease. An important amount of preclinical data suggested the possible application of A(2A) receptor antagonists in Parkinson's disease, particularly as adjuvant therapy to the currently used dopaminergic agonists. Several A(2A) receptor antagonists are currently in clinical trials in patients with Parkinson's disease and initial results have been promising. In recent years, many pharmaceutical companies have started programs to develop A(2A) antagonists for Parkinson's disease and for other indications, such as neurodegenerative diseases in general, depression and restless legs syndrome. Antagonists with high A(2A) receptor affinity and selectivity have been developed from various chemical classes of compounds, including xanthines, adenines and other amino-substituted heterocyclic compounds. Novel structures include benzothiazole and thiazolopyridine derivatives. The present review describes properties of standard A(2A) receptor antagonists including those in clinical development. Furthermore, the different chemical classes of A(2A) receptor antagonists that have been described in the literature, including recent patent literature, will be presented.