Natural antisense RNAs are endogenous molecules that are complementary to RNA transcripts of already established function. They were discovered first in prokaryotes in which they are now recognised as an important component of molecular mechanisms involved in the regulation of gene expression. Recently, through the cumulative efforts of molecular biologists and bioinformaticians, natural antisense RNAs have been demonstrated in significant numbers in eukaryotic systems also. Probably the most exciting outcome of these studies is that natural antisense RNAs are particularly prevalent in the nervous system. Here we discuss the major known types of natural antisense RNAs in eukaryotic systems and focus on their potential roles in the regulation of gene expression in the brain.