Epitranscriptomics is an exciting emerging area that studies biochemical modifications of RNA. The field is boosted by the technical efforts of the last decade to characterize and quantify RNA modifications which have led to a map of post-transcripcional RNA marks in normal cell fate and develoment. However, the scientific interest has been fueled by the discovery of aberrant epitranscriptomes associated with human diseases, mainly cancer. The challenge is now to see whether epitrancriptomics offers a tunable mechanims to be targeted by small- molecule intervention. In this review, we will describe the principal RNA modifications (with a focus on mRNA), summarize the latest scientific evidences of their dysregulation in cancer and provide an overview of the state-of-the-art drug discovery to target the epitranscriptome. Finally, we will discuss the principal challenges in the field of chemical biology and drug development to increase the potential of targeted-RNA for clinical benefit.