Stroke is one of the leading causes of death and disability in developed countries. Since protecting neurons alone is not sufficient for stroke therapy, research has shifted to the rescue of multiple cell types in the brain. In particular, attention has focused on the study of how cerebral blood vessels and brain cells communicate with each other. Recent findings suggest that cerebral endothelial cells may secrete trophic factors that nourish neighboring cells. Although data are strongest in terms of supporting endothelial–neuronal interactions, it is likely that similar interactions occur in white matter as well. In this mini-review, we summarize recent advances in the dissection of cell–cell interactions in white matter. We examine two key concepts. First, trophic interactions between vessels and oligodendrocytes (OLGs) and oligodendrocyte precursor cells (OPCs) play critical roles in white matter homeostasis. Second, cell–cell trophic coupling is disturbed under diseased conditions that incur oxidative stress. White matter pathophysiology is very important in stroke. A deeper understanding of the mechanisms of oligovascular signaling in normal and pathologic conditions may lead us to new therapeutic targets for stroke and other neurodegenerative diseases.