The Zika virus (ZIKV) epidemic has recently emerged as a public health threat due to its teratogenic nature and association with the serious neurological condition Guillain-Barré syndrome (GBS). To date, no approved antiviral therapeutics to treat, nor vaccines to prevent, ZIKV infection are available. In order to develop effective anti-ZIKV vaccines, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. In this paper, we discuss the recent progress in developing vaccines against ZIKV and the hurdles to overcome in making efficacious anti-ZIKV vaccines. Here, we propose strategies to make efficacious and safe vaccines against ZIKV by using novel approaches including molecular attenuation of viruses and TLR-based nanoparticle vaccines. The question of exacerbating dengue virus infection or causing GBS through the production of cross-reactive immunity targeting viral or host proteins have been addressed in this paper. Challenges in implementing immunogenic and protective ZIKV vaccine trials in immunodepressed target populations (for example, pregnant women) have also been discussed.