Accumulating findings indicate that nucleotides play an important role in microglia through P2 purinoceptors. P2 purinoceptors are divided into two families, ionotropic receptors (P2X) and metabotropic receptors (P2Y). P2X receptors (7 types; P2X(1) - P2X(7)) contain intrinsic pores that open by binding with ATP. P2Y receptors (8 types; P2Y(1, 2, 4, 6, 11, 12, 13 and 14)) are activated by nucleotides and couple to intracellular second-messenger systems through heteromeric G-proteins. Nucleotides are released or leaked from non-excitable cells as well as neurons in physiological and pathophysiological conditions. Microglia express many types of P2 purinoceptors and are known as resident macrophages in the CNS. ATP and other nucleotides work as 'warning molecules' especially through activating microglia in pathophysiological conditions. Microglia play a key role in neuropathic pain, chemotaxis and phagocytosis through nucleotide-evoked activation of P2X(4), P2Y(12) and P2Y(6) receptors, respectively. These findings indicate that extracellular nucleotides are important players in the central stage of microglial function.