Highly pathogenic avian influenza (HPAI) circulates among wild waterfowl and can infect humans through zoonotic transmission. HPAI, subtype H5N1, emerged in humans in 1997 without any reassortment with a human influenza strain. The absence of avian influenza receptors in the upper airway could explain the lack of efficient human-to-human transmission of H5N1. Avian influenza viruses in humans are thought to have a longer incubation period than human influenza viruses, with most cases occurring 2–4 days following exposure during the initial outbreak in 1997 and a longer range of up to eight days following exposure in later infections. Neurotropism of avian influenza has been described in naturally susceptible populations of avian species as well as in mammalian species such as domestic cats, tigers, leopards, mice, and others. Avian influenza infection in humans has resulted in high serum levels of proinflammatory cytokines and chemokines as well as exaggerated inflammatory responses when compared to seasonal influenza, sometimes referred to as “cytokine storm.”.