Zika virus (ZIKV) emerged as a global health threat due to its association with severe outcomes in humans, including microcephaly and other neurological complications. ZIKV replication and induction of neuronal death are considered key factors for severe ZIKV-induced disease. Understanding the pathogenic mechanisms induced by ZIKV infection is crucial to identify potential therapeutic targets that may prevent or at least minimize the consequences in early phases of disease and adulthood. This chapter will discuss how ZIKV emerged in the past few years, will describe some aspects of the infection and, finally, will focus on the evidence of neuropathological mechanisms of the disease in humans and experimental models and its potential neuropsychiatric outcomes. The mechanisms explored are: (i) infection and virus replication, activation and apoptosis of neural progenitor cells, mature neurons and glial cells with concomitant induction of neuroinflammation; (ii) induction of neuronal excitotoxicity; and (iii) autophagy modulation during ZIKV infection.