Modification of adenosine to N6-methyladenosine (m6A) is a common post-transcriptional modification in most eukaryotic RNAs (including mRNA and miRNA); it regulates the stabilization of mRNA, its transport from the nucleus to the cytosol and its translational efficiency. Sperm formation is known to be associated with regulated changes in gene expression occurring before and during spermatogenesis. Several mechanisms operating in the testis to control gene expression are essential for the generation of sperm-specific transcripts and proteins. Recent information now documents key roles for m6A modification of RNA in testis. Gene knockout and mutations in methylases (writers) and demethylases (erasers) have been shown to result in male infertility. The intersection of two lines of investigation resulted in the discovery that FTO, one of two m6A erasers, appears to be regulated by the signaling enzyme GSK3α. Targeted disruption of GSK3α or its conditional knockout in developing spermatogenic cells results in male infertility. Epididymal maturation and the ability of sperm to fertilize eggs are impaired in knockout mice. Also, studies on signaling mechanisms underlying the maintenance of stem cell pluripotency identified a novel mechanism involving m6A demethylation by FTO and its regulation by GSK3. These two lines of evidence prompted preliminary studies which showed the presence of FTO, its binding to GSK3α, and reduction in the levels of m6A RNA in the testis of GSK3α knockout mice. Taken together these data form the basis for the hypothesis that regulation of FTO by GSK3α in developing spermatocytes and spermatids is essential for normal sperm function and male fertility.