This special edition of the Journal of Neuroimmune Pharmacology focuses on the leading edge of metabolomics in brain metabolism research. The topics covered include a metabolomic field overview and the challenges in neuroscience metabolomics. The workflow and utility of different analytical platforms to profile complex biological matrices that include biofluids, brain tissue and cells, are shown in several case studies. These studies demonstrate how global and targeted metabolite profiling can be applied to distinguish disease stages and to understand the effects of drug action on the central nervous system (CNS). Finally, we discuss the importance of metabolomics to advance the understanding of brain function that includes ligand-receptor interactions and new insights into the mechanisms of CNS disorders.