The "Operon paper" by F. Jacob and J. Monod started 50 years of research into understanding how the expression of genes is regulated on a molecular level. Ten years ago, microRNAs (miRNAs) emerged as major regulators of eukaryotic gene expression. Here, I will review the basic principles of gene regulation by miRNAs and how these principles can be linked to insights from the Operon paper. A lot of what is understood about miRNAs required a combination of computational and experimental methods. I will discuss some examples that illustrate the power of this approach.