The dramatic intertumoral and intratumoral heterogeneity in glioblastoma represents a formidable obstacle to finding effective combination targeted therapy for each individual patient. The article by Wang and colleagues in this issue of Cancer Discovery adds to a growing body of literature that points to these diverse aberrant genomes coalescing onto a very limited number of cellular states, reviving the hope of eventually identifying and therapeutically targeting just a few central gene-regulatory targets in most gliomas.See related article by Wang et al., p. 1708.