Oligodendrocytes are highly specialized neural cells that produce myelin, essential for rapid electrical conduction of neural signals in the central nervous system (CNS). The emergence of oligodendrocytes and myelin was a critical step in the evolution of vertebrates and fundamental for the development of the mammalian connectome, and indispensable for miniaturization and enhanced computing power of the brain. The advance in cognitive capacity is paralleled by increasing eminence of white matter, composed of interconnected bundles of myelinated axons; white matter volume increases from 6% of the brain in shrews, considered related to the most primitive mammals, up to 50% in Homo sapiens. Myelinating oligodendrocytes together with smaller populations of oligodendrocyte precursor cells (OPCs) and satellite or perineuronal oligodendrocytes account for more than half the glial cells in the human brain. Together, these three cell types make up the oligodendroglial cell lineage that express common lineage specific proteins and transcription factors and display a degree of molecular and functional diversity. OPCs are the most numerous oligodendroglial cells during developmental axonal myelination, which extends postnatally for many years in humans. The generation of myelinating oligodendrocytes from OPCs throughout life continues to be important for adaptive plasticity of neural circuits and myelination of new axons required for learning. Myelination decreases in the aging brain and correlates with natural or physiological age-related cognitive decline. Like all neural cells, oligodendroglia express a wide assortment of ion channels, transporters, and neurotransmitter receptors that are essential for maintaining neuronal signaling, principally myelination, axonal metabolic support and homeostatic regulation of the periaxonal microenvironment. Notably, OPCs are unique amongst neuroglia in that, like neurons, they are electrically excitable and form synapses with neurons. Oligodendroglial cells also contribute to neuroplasticity through multiple mechanisms including axon guidance, synapse formation and adaptive myelination. In short, oligodendroglia are essential for normal CNS integrity, cognitive function and behavior.