Avian influenza is an important zoonotic disease that has become endemic in Southeast Asia and in the case of highly pathogenic H5N1 has caused significant human mortality and morbidity. Avian influenza virus (AIV) infections may be asymptomatic or present as mild conjunctivitis in humans; however, H5N1 infections may present as severe pneumonia progressing to acute respiratory disease syndrome, multiorgan dysfunction syndrome and death. Since 2003, there have been a total of 436 cases and 262 deaths due to H5N1 infections. The number of cases has decreased steadily since 2006; however, the emergence of multiple genetically distinct sublineages of H5N1 has continued. These emerging sublineages display varying levels of drug resistance and in some cases an increased preference for binding to human α2,6-linked sialic acid cellular receptors. Though H5N1 has not shown efficient transmissibility between humans, the rapid evolution of the virus presents a concern for the emergence of a virus with this capability. Here we review the epidemiology, host range, clinical features, prophylaxis and treatment options, and preventative measures recommended for AIV with an emphasis on H5N1.