Many surface proteins of Gram-positive bacteria are anchored to the cell wall by the action of sortase enzymes, a recently discovered family of cysteine transpeptidases. As the surface proteins of pathogens are frequently required for virulence, the sortase might be a suitable target for the development of anti-Gram-positive drugs. Recently, the mechanism and active sites of sortase was elucidated by the research of sortaseA(SrtA) in Staphylococcus aureus and a series of SrtA inhibitors have been identified for providing the basis for further development of potent inhibitors.