Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and humans have raised concerns that a new influenza pandemic will occur in near future. Currently, four antivirals have proven efficacy in the treatment and prophylaxis of influenza A infections: two M2 inhibitors (amantadine and rimantadine) and two neuraminidase inhibitors (zanamivir and oseltamivir). Early treatment with antivirals reduces the duration of symptoms and the time to recovery by one to two days. However, when antivirals are used for the treatment the antiviral resistance develops rapidly, limiting their use. There is an urgent need for research on newer antiviral agents and "universal" vaccine against influenza virus. The M2 protein from the influenza A virus forms a proton channel in the virion and is essential for infection. As a relatively conserved protein, the M2 protein seems to be a suitable candidate for development of a new generation of vaccine or antiviral agents. This review describes the role of the M2 ion channel in virus replication and the structure-function relationship of the channel.