DNA methylation is an epigenetic modification that is generally associated with repression of transcription initiation at CpG-island promoters. Here we argue that, on the basis of recent high-throughput genomic and proteomic screenings, DNA methylation can also have different outcomes, including activation of transcription. This is evidenced by the fact that transcription factors can interact with methylated DNA sequences. Furthermore, in certain cellular contexts, genes containing methylated promoters are highly transcribed. Interestingly, this uncoupling between methylated DNA and repression of transcription seems to be particularly evident in germ cells and pluripotent cells. Thus, contrary to previous assumptions, DNA methylation is not exclusively associated with repression of transcription initiation.