Our understanding of the complexity of nervous system cancers has been enhanced through the incorporation of cellular heterogeneity into tumor models, with cellular subsets displaying stem cell characteristics. Advanced cancers such as glioblastoma are organized in a hierarchy with cancer stem cells at the apex. Cancer stem cells are functionally defined by their ability to self-renew and propagate tumors similar to the parental tumors from which they are derived. We will discuss advances in cancer stem cells, including the ability to prospectively isolate and interrogate cancer stem cells, by defining molecular mechanisms responsible for the tumor maintenance and growth. While the field of cancer stem cell biology is relatively young, continued elucidation of the tumor hierarchy holds promise for the development of novel patient therapies.