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This paper analyses the publicly available data on the distribution and evolution of highly pathogenic avian influenza virus (HPAIV) H5N1 clades, whilst acknowledging the biases resulting from the nonrandom selection of isolates for gene sequencing. The data indicate molecular heterogeneity in the global distribution of HPAIV H5NI, in particular in different parts of East and Southeast Asia. Analysis of the temporal pattern of haemagglutinin clade data shows a progression from clade 0 (the 'dominant' clade between 1996 and 2002) to clade 1 (2003-2005) and then to clade 2.3.4 (2005 onwards). This process continuously produces variants, depending on the frequency of virus multiplication in the host population, which is influenced by geographical variation in poultry density, poultry production systems and also HPAI risk management measures such as vaccination. Increased multilateral collaboration needs to focus on developing enhanced disease surveillance and control targeted at evolutionary 'hotspots'. [ABSTRACT FROM AUTHOR]