The prevention and control of influenza with vaccines and antiviral drugs is of great importance. M2 inhibitors, amantadine and rimantadine have been extensively used in some countries. The next generation of antiviral drugs, neuraminidase (NA) inhibitors oseltamivir and zanamivir, are being stockpiled for a potential influenza pandemic. The emergence of resistant strains is thus an important issue. The purpose of this study was to examine the sensitivity to M2 and NA inhibitors of Greek influenza A(H3N2) strains isolated during three influenza seasons between 2004 and 2008 and to determine the phylogenetic clades of those strains. M2 and NA sequences of 34 patient isolates were checked for known resistance mutations. In addition, haemagglutinin (HA) sequences were used to determine the phylogenetic relationship between resistant and sensitive strains. All influenza A(H3N2) strains isolated during the season 2004-5 were found susceptible to adamantanes, bearing the S31N mutation, compared to 88% of the strains isolated in 2005-6 and 75% of the strains isolated in 2006-7. Molecular analysis of the HA gene showed a correlation of the mutants with specific phylogenetic clades. No known mutations in the NA or HA gene that have been implicated in resistance to NA inhibitors were found in the A(H3N2) strains isolated in the three influenza seasons. Despite the fact that amantadine is the only drug approved for prophylaxis in Greece, it has not been extensively used. So it seems that resistant strains circulating in the area after 2005 followed the global trend of replacement of susceptible strains by resistant ones. Oseltamivir and zanamivir are currently approved only for therapeutic use in Greece and has not been extensively used either.