Clinical and epidemiological surveillance of influenza and other Acute Respiratory Infections (ARI) are currently a major objective of Public Health. The aim was to describe the epidemiology of influenza using the Italian surveillance system. Vaccination Coverage (VC) rates were calculated during 1999-2009 influenza seasons. Molecular studies of influenza virus isolated, from patients with ILI, living in Apulia, are described. 1269 nasal-pharyngeal swabs were taken from patients with ILI and ARI in order to isolate and identify viruses using PCR. Influenza isolates are typed as being types A and B and influenza A isolates are A/H1 and A/H3. The progression of the ILI cases registered in Apulia was similar to the data recorded on a national level. The VC data recorded in Apulia showed a progressive increase in the vaccine doses administered to subjects over 65 years old. The virological surveillance showed a major circulation of the type A/H3N2 influenza virus during the peak incidence of the illness in seasons 1999-2000, 2002-2003, 2004-2005 and 2008-2009. During the same period, the lowest incidence was registered when the type A/H1N1 and B viruses were in circulation. In contrast, during the other seasons the lowest incidence was reported with A/H3N2 and B viruses.