Although the field of protein methylation enjoys widespread interest in the scientific literature of today, this is a recent phenomenon. Papers on 'protein methylation' were first published in the 1960s. By the early 1980s, it was known that lysine, arginine, histidine and dicarboxylic amino acids were post-translationally methylated by highly specific methyltransferases. However, despite these early advances, the biological importance of these reactions remained largely unproven. With the introduction of modern molecular biology techniques in the mid-1990s, an enormous surge of interest in protein methylation occurred. It is now clear that protein methylation carries many important biological functions, including gene regulation and signal transduction. Thus, the story of protein-methylation research is a testament to both modern molecular biology and the importance of continuing to pursue lines of research in which the precise biological function might not be currently known.