Design of novel H5N1 inhibitors is currently a research topic of vital importance owing to both a recent pandemic threat by the worldwide spread of H5N1 avian influenza and the high resistance of H5N1 virus to the most widely used commercial drug, oseltamivir-OTV (Tamiflu). There has been much progress in this field recently. This review covers recent work on bioinformatics studies, structure based design, computer modeling and molecular dynamics simulations.