The epitranscriptomics field has undergone tremendous growth since the discovery that the RNA N⁶-methyladenosine (m⁶A) modification is reversible and is distributed throughout the transcriptome. Efforts to map RNA modifications transcriptome-wide and reshape the epitranscriptome in disease settings have facilitated mechanistic understanding and drug discovery in the field. In this review we discuss recent advancements in RNA modification detection methods and consider how these developments can be applied to gain novel insights into the epitranscriptome. We also highlight drug discovery efforts aimed at developing epitranscriptomic therapeutics for cancer and other diseases. Finally, we consider engineering of the epitranscriptome as an emerging direction to investigate RNA modifications and their causal effects on RNA processing at high specificity.