Zika virus is an emerging flavivirus that causes the neurodevelopmental congenital Zika syndrome and that has been linked to the neuroinflammatory Guillain-Barré syndrome. The absence of a vaccine or a clinically approved drug to treat the disease combined with the likelihood that another outbreak will occur in the future defines an unmet medical need. Several promising drug candidate molecules have been reported via repurposing studies, high-throughput compound library screening, and de novo design in the short span of a few years. Intense research activity in this area has occurred in response to the World Health Organization declaration of a Public Health Emergency of International Concern on February 1, 2016. In this Perspective, the authors review the emergence of Zika virus, the biology of its replication, targets for therapeutic intervention, target product profile, and current drug development initiatives.