INTRODUCTION The current avian and human H5N1 influenza epidemic has been in resurgence since 2004. We decided to evaluate published evidence in relation to epidemiology, clinical features and course, laboratory diagnosis, treatment and outcome of human H5N1 influenza, and develop institutional clinical management guidelines. METHODS A search of PubMed was conducted for all English language articles with search terms "avian", "influenza" and "H5N1". The bibliography of articles was searched for other references of interest. RESULTS Published case series from Hong Kong in 1997, and Thailand and Vietnam since 2004 have indicated a rapidly progressive primary viral pneumonia resulting in acute respiratory distress syndrome. The majority of human H5N1 infections can be linked to poultry exposure. Hitherto there has been no evidence of efficient human-to-human transmission. Case fatality rates have varied from 71% in Thailand to 100% in Cambodia. Oseltamivir appears to be the only potentially effective antiviral therapy. H5N1 isolates in Vietnam have become resistant to oseltamivir, resulting in persistent viral replication and death. There is as yet no effective human H5N1 vaccine. CONCLUSIONS National and international preparedness plans are well advised. Clinical trials to evaluate higher dose oseltamivir therapy and immunomodulatory treatment are urgently needed.