The MYC family plays essential roles during brain development and their oncogenic deregulation is implicated in the formation of embryonal neural tumors such as medulloblastomas (MB) and neuroblastoma (NB). Amplification of the MYCN is the predominant marker for aggressive NB and correlates with poor prognosis, while c-MYC overexpression is a defining feature of MB subgroups inflected with aggressive biological behavior and increased likelihood of metastasis. Not surprisingly MYC has emerged as an attractive target for pediatric neural cancer therapy. However despite three decades of intensive research in MYC biology and an impressive number of 30,000 publications, inhibition of MYC as therapeutic strategy remains an elusive goal in cancer medicine. This review discusses the potential and challenges of targeting the oncogenic effects of MYC as therapeutic strategy for MYC over-expressing embryonal neural tumors where current therapies are inadequate.