Epigenetic modifications and particularly the methylation of cytosines 5' of guanine residues (CpGs) in gene promoter regions is an essential regulatory mechanism for normal cell development. DNA methylation can inactivate tumor suppressor genes by inducing C > T transitions in somatic and germline cells and by altering gene transcription. On the other hand, hypomethylation of specific sequences may reactivate the expression of potential oncogenes. Thus, aberrant hyper- and hypomethylation are considered crucial steps leading to cancer development. Until recently, differently from most adult tumors, only limited information was available on the methylation aberrations in neuroblastoma. In the last 2 years, however, this situation has drastically changed and many information has been gained on the relevance of methylation in this tumor. In this review, we summarize the latest findings on the role of methylation in neuroblastoma and in particular to its clinical significance.