The development of dendritic cells (DCs) from progenitor cells is associated with mitochondrial biogenesis, which is driven by peroxisome proliferator-activated receptor-γ (PPARγ) co-activator 1α (PGC1α) and promoted by PPARγ, mammalian target of rapamycin (mTOR) and MYC. Differentiated DCs populate their niches as immature DCs. Immature DCs use fatty acid oxidation as a core metabolic process. Activation of DCs by Toll-like receptor (TLR) agonists leads to a rapid increase in flux through glycolysis and the associated pentose phosphate pathway, with an accompanying increase in spare respiratory capacity and fatty acid synthesis. These metabolic changes are initiated by a pathway downstream of TLRs that involves AKT, TANK-binding kinase 1 (TBK1), inhibitor of nuclear factor-κB kinase subunit-ε (IKKε) and hexokinase 2 (HK2), and they are crucial for DC activation. After being activated, DCs remain glycolytic. This process is essential for continued DC survival and is controlled by mTOR and hypoxia-inducible factor 1α (HIF1α). CDP, committed DC progenitor; OXPHOS, oxidative phosphorylation.