Neural stem cells (NSCs) derive from the neuroepithelium of the neural tube, develop into radial glial cells, and recede at later developmental stages. In the adult, late descendants of these embryonic NSCs reside in discretely confined areas of the central nervous system, the stem cell niches. The best accepted canonical niches are the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus of the hippocampus. Stem cell niches provide a privileged environment to NSCs that supports self-renewal and maintenance of this cellular compartment. While numerous studies have highlighted the importance of transcription factors, morphogens, cytokines, and growth factors as intrinsic and extrinsic factors of stem cell regulation, less attention has been paid to the molecular micromilieu that characterizes the stem cell niches. In this chapter, we summarize increasing evidence that the extracellular matrix (ECM) of the stem cell environment is of crucial importance for the biology of this cellular compartment. A deeper understanding of the molecular composition of the ECM, the complementary receptors, and the signal transduction pathways engaged may prove highly relevant for harnessing NSCs in the context of biotechnological applications.