Based on hemagglutinin (HA) and neuraminidase (NA), influenza A virus is divided into 18 different HA (H1 to H18) and 11 NA types (N1 to N11), opening the possibility for reassortment between the HA and NA genes to generate new HxNy subtypes (where x could be any HA and y is any NA, possibly). In recent four years, since 2010, highly pathogenic avian influenza (HPAI) viruses of H5N1 subtype (HPAI A/H5N1) have become highly enzootic and dynamically evolved to form multiple H5 HA clades, particularly in China, Vietnam, Indonesia, Egypt, Cambodia, and Bangladesh. So far, after more than 10 years emerged in Vietnam (since late 2003), HPAI A/H5N1 is still posing a potential risk of causing outbreaks in poultry, with high frequency of annual endemics. Intragenic variation (referred to as antigenic drift ) in HA (e.g., H5) has given rise to form numerous clades, typically marking the major timelines of the evolutionary status and vaccine application in each period. The dominance of genetically and antigenically diversified clade 2.3.2.1 (of subgroups a, b, c), clade 1.1 (1.1.1/1.1.2) and re-emergence of clade 7.1/7.2 at present, has urged Vietnam to the need for dynamically applied antigenicity-matching vaccines, i.e., the plan of importing Re-6 vaccine for use in 2014, in parallel use of Re-1/Re-5 since 2006. In this review, we summarize evolutionary features of HPAI A/H5N1 viruses and clade formation during recent 10 years (2004-2014). Dynamic of vaccine implementation in Vienam is also remarked.