Zika virus is a flavivirus known to cause microcephaly during development. The mechanism underlying Zika virus-induced neuropathogenesis is still poorly understood. Recent studies have utilized the cutting edge cell culture and animal model technologies to elucidate factors contributing to Zika virus-associated microcephaly. While future work is needed, current studies have suggested three main factors that contribute to Zika virus pathology: viral lineage, host immunity, and pregnancy stages. This mini review will focus on some of the recent findings that advanced our knowledge in Zika virus-associated microcephaly.