The worldwide attention that the Zika virus (ZIKV) attracted, following its declaration as a Public Health Emergency of International concern by WHO in 2016, has led to a large collective effort by the international scientific community to understand its biology. Despite the mild symptoms caused by ZIKV in most infected people, the virus displays a number of worrying features, such as its ability to cause transplacental infection, fetal abnormalities and vector independent transmission through body fluids. In addition, the virus has been associated with the induction of Guillain-Barre syndrome in a number of infected individuals. With travelling, the virus has spread outside the original ZIKV endemic areas making it imperative to find ways to control it. Thus far, the large number of animal models developed to study ZIKV pathogenesis have proven to be valuable tools in understanding how the virus replicates and manifests itself in the host, its tissue tropism and the type of immune responses it induces. Still, vital questions, such as the molecular mechanisms of ZIKV persistence and the long-term consequences of ZIKV infection in the developing brain, remain unanswered. Here, we reviewed and discussed the major and most recent findings coming from animal studies and their implications for a ZIKV vaccine design.