The creation and characterization of permanent cell lines derived from primary human gliomas in the 1960s gave scientists access to unlimited, renewable material in which to study the development of brain tumors. These cells, however, were already tumorigenic and selected for growth in culture, limiting the amount of information that could be gathered about the events that led to the formation of their tumors of origin. In response to these limitations, investigators moved to the study of primary tumors to identify in a correlative fashion the lesions important in tumor formation, and to the use of animal models to gain information about the transformation process. While these approaches have been unarguably successful, they too are limited by their correlative nature (in the case of cytogenetic studies) and their potential lack of direct relevance to human cancer (in the case of mouse models). Recent developments in the isolation and manipulation of human cells have allowed investigators a fresh chance to address questions about brain tumors in a direct fashion. The present review serves as a summary of important recent findings derived from the use of defined human cells in the study of gliomas.