Post-translational modification (PTM) of proteins is vital for increasing proteome diversity and maintaining cellular homeostasis. If the writing, reading, and removal of modifications are not controlled, cancer can develop. Arginine methylation is an understudied modification that is increasingly associated with cancer progression. Consequently protein arginine methyltransferases (PRMTs), the writers of arginine methylation, have rapidly gained interest as novel drug targets. However, for clinical success a deep mechanistic understanding of the biology of PRMTs is required. In this review we focus on advances made regarding the role of PRMTs in stem cell biology, epigenetics, splicing, immune surveillance and the DNA damage response, and highlight the rapid rise of specific inhibitors that are now in clinical trials for cancer therapy. Arginine methylation as a PTM has gained considerable interest since the recent discovery that solid and haematological cancers display elevated expression of PRMTs, which correlates with poor patient prognosis.Several new findings have cemented arginine methylation as a key regulator of processes hijacked by the cancer cell to ensure survival, including epigenetic-mediated gene expression, mRNA splicing, and the DNA damage response.Growing appreciation of the important role of PRMT5 in cancer stem cell function provides an exciting therapeutic prospect.The development of specific PRMT inhibitors has proceeded at an unprecedented pace, resulting in three major pharmaceutical companies entering their own PRMT inhibitors into Phase I trials. Drug targeting of arginine methylation is becoming a real clinical prospect.