Since isolation of Zika virus (ZIKV) in Uganda from Zika forest in the 1947, for sixty years the virus has caused only scattered human cases in Africa and Southeast Asia. From 2007, outbreaks with an increasing number of cases, including cases with neurological manifestations, have been occurring in Pacific islands. In 2015, ZIKV reached Brazil with an explosive number of cases and a severe neurological impact on fetuses and newborns. The natural history and several immunological aspects of ZIKV infection need to be characterized. In this review it is summarized the spread of ZIKV around the world and pointed out some gaps on the immunological knowledge related to the infection. The characterization of the immunodominant/protective immune response would contribute to vaccine and diagnosis tests development.