In an earlier study, we explored the in vitro antiviral activity and synergy of single, double, and triple combinations of amantadine, ribavirin and oseltamivir against a panel of influenza A viruses that were susceptible to these drugs [10] . Our hypothesis was that a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action, and which act at different stages in the viral life cycle, could result in synergistic antiviral activity. Our results showed that these drugs did indeed act synergistically, with the triple combination showing significantly greater synergy than any of the double combinations evaluated. Furthermore, we found that the synergy of the TCAD regimen was maintained across multiple seasonal and avian influenza A strains, including the three major subtypes -A/H1N1, A/H3N2, and the avian A/H5N1 -that currently cause significant morbidity and mortality in humans.