The conserved RNA-binding protein Hfq, originally discovered in Escherichia coli as a host factor for Qbeta replicase, has emerged as a pleiotropic regulator that modulates the stability or the translation of an increasing number of mRNAs. During the past 5 years, Hfq-mediated control has been an area of increasing focus because the protein has been linked to the action of many versatile RNA-based regulators that use basepairing interactions to regulate the expression of target mRNAs. The recent findings that Hfq assists in bimolecular RNA-RNA interactions and is similar structurally and functionally to eukaryotic Sm proteins have further fueled interest in this important post-transcriptional regulator. Here, we summarize the history of Hfq and highlight results that have led to an important gain in insight into the physiology, biochemistry and evolution of Hfq and its homologues.