Approximately 2 years have passed since the detection of the first human case of West Nile virus (WNV) infection in Greece, which was the starting signal of a large outbreak in 2010, followed by a second one in 2011. More than 250 neuroinvasive disease cases with 15% fatality were observed during the two WNV seasons. WNV lineage 2 sequences were obtained from blood donors, Culex mosquitoes, wild birds and sentinel chickens. The Greek WNV strain shows high genetic relatedness to the goshawk-Hungary/04 WNV strain; an amino acid substitution in nonstructural protein 3 (H249P) is observed, which has been previously associated with increased virus transmission. This article provides an overview of the WNV outbreaks in Greece and discusses the knowledge gained from these events.