AbstractInfluenza is a long‐standing health problem. We review here the recent development of neuraminidase inhibitors for influenza treatment. Tamiflu, the phosphate salt of oseltamivir, is an orally available neuraminidase inhibitor designed to have a cyclohexene scaffold to mimic the structure of the oxoniumlike intermediate in the enzymatic cleavage of the terminal sialoside from cell receptor. Many new synthetic procedures of oseltamivir without using shikimic acid have been explored because the current industrial manufacture of tamiflu may have problem in shortage of shikimic acid for global supply during influenza pandemics. In these shikimate‐independent syntheses, six different approaches have been utilized to construct the multiple substituted cyclohexene ring: (i) using existing six‐membered rings, (ii) construction by Diels—Alder reactions, (iii) construction by intramolecular aldol, Dieckmann and Wittig reactions, (iv) construction by tandem Michael—Wittig reactions, (v) construction by olefin metathesis, and (vi) construction by Claisen rearrangement. Phosphonate group is generally used as a bioisostere of carboxylate in drug design. The syntheses of tamiphosphor and zanaphosphor, which are the phosphonate congeners of oseltamivir and zanamivir, were recently accomplished and shown to possess potent inhibitory activities against avian and human influenza viruses, including the oseltamivir‐resistant strain, according to the neuraminidase inhibition, cell‐based assay and mice experiments. For the first time, phosphonate monoalkyl esters are proved to be real active drugs, but not prodrugs of the parental phosphonic acids. This review covers the design, synthesis and biological activity of phosphonate compounds as effective anti‐influenza agents.