Fic proteins are a family of proteins characterized by the presence of a conserved FIC domain that is involved in the modification of protein substrates by the addition of phosphate-containing compounds, including AMP and other nucleoside monophosphates, phosphocholine and phosphate. Fic proteins are widespread in bacteria, and various pathogenic species secrete Fic proteins as toxins that mediate post-translational modifications of host cell proteins, to interfere with cytoskeletal, trafficking, signalling or translation pathways in the host cell. In this Review, we discuss the current knowledge of the structure, function and regulation of Fic proteins and consider important areas for future research.