The central nervous system (CNS) is an immune-privileged site with tightly-regulated immune responses, a concept proposed by Nobel Laureate Sir Peter Medawar in 1960. Under physiological conditions, only a few T lymphocytes conducting immunosur-veillance can infiltrate the CNS. However, in neurodegenerative pathology such as multiple sclerosis (MS), a devastating inflam-matory demyelinating disease, transmigration of encephalitogenic T cells from the periphery to the CNS is evident, contributing to the etiology of MS. Among the encephalitogenic T cells, in recent years, interleukin-17-producing T helper 17 (TH17) cells have at-tracted intensive research interests because of their superior ability to induce MS, as compared to the interferon-γ-producing T helper 1 (TH1) cells that had long been regarded as the primary culprit in the pathogenesis of MS, prior to the discovery of TH17 cells in 2005. An early study showed that C-C chemokine receptor 6 (CCR6)+ TH17 cells are the first encephalitogenic T cells to infiltrate the CNS, which leads to the second wave of infiltration by other neuroinflammatory immune cells including TH1 cells (Reboldi et al., 2009). These T cells drive the development of clinical signs of MS. Conversely, forkhead box P3 (Foxp3)+ regulatory T (Treg) cells suppress TH17 and TH1 cells, mitigating neuroinflammation in MS. Intriguingly, a recent study showed that Treg cells can actually promote remyelination, a key event in neural regeneration (Dom-browski et al., 2017). Analogous to the well-established dichotomy of TH1 and interleukin-4-producing T helper 2 cells, TH17 and Treg cells are considered dichotomous cell fates of activated CD4+ T cells, because of the intimate physical and functional interactions of their master transcriptional factors (retineic-acid-receptor-related orphan nuclear receptor-γ (RORγt) and Foxp3) and the dynamic two-way transdifferentiation between them in various pathogenic conditions. While immune signals (TCR ligation, CD28-mediated co-stimulation, and cytokine) seemingly orchestrate the differenti-ation of these T cell subsets, an emerging frontier in immunology research is the realization that at a fundamental level, it is the cellu-lar metabolism that dictates the T cell fate decisions including TH17 vs. Treg. To this end, TH17 cells primarily engage glycolysis and fatty acid synthesis (FAS), while Treg cells mainly use oxidative phos-phorylation and fatty acid oxidation (FAO) to satisfy their bioener-getic and biosynthetic demands. This suggests that targeting these metabolic pathways may offer a legitimate approach to cure MS by suppressing neurodegenerative TH17 and concomitantly promoting neuroregenerative Treg cells. Thus, in this perspective, we focus on metabolic checkpoints capable of tipping the TH17/Treg balance in favor of Treg formation.