Neural stem cells (NSC) are a tissue-specific subtype of self-renewing and multipotent cells that can give rise to all neural populations. In this review, the importance of maintaining cell–cell contacts in the study of NSC is highlighted, and data obtained from some crucial single-cell studies is compared to results obtained from neurospheres, where aggregates of NSC are grown in suspension. In particular, results that indicate how this culture system may be well suited to analyze NSC plasticity, cell–cell, and cell–extracellular matrix (ECM) interactions are pointed out, and the hypothesis that cell–cell and cell–ECM contacts may be essential for NSC maintenance, survival, and proliferation is highlighted. Finally, it is suggested that neurospheres might play a role in the study of context-dependent behavior of NSC in niches by providing a system where NSC can be challenged chemically or biologically and analyzed in vitro, in a time- and context-dependent manner. © 2004 Wiley-Liss, Inc.