Charles DeLisi is partially supported by NIH grants A08 POGM66401A and J50 01-130021. Daniel S. Roberts is supported by NIH training grant 2T32 GM00854. Shelley J Russek is supported by NIH/NINDS Grant NS050393. Funding to pay the Open Access publication charges for this article was provided by the Boston University Bioinformatics Program. The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries BACKGROUND: With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. METHODOLOGY/PRINCIPAL FINDINGS: We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. CONCLUSIONS/SIGNIFICANCE: Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions. A new highly pathogenic strain of avian influenza, H5N1, emerged in the poultry markets of Hong Kong in 1997 and subsequently re-emerged in Vietnam in 2003. From this time onwards it has rapidly spread across the globe and is likely to be endemic in poultry in many parts of the world. Although onward transmission to humans at present remains limited, the high case fatality rate in those people that are infected has raised concerns about the impact of a potential human pandemic [1, 2] . Whilst much research and planning is currently underway to contain any outbreak in humans, relatively little is known about the extent of infection in poultry and, in particular, the transmissibility of highly pathogenic avian influenzas between poultry farms. Such understanding is vital if we are to limit the potential for a human pandemic by reducing the extent of infection in poultry, either through movement restrictions, culling or vaccination.