Zika virus, a flavivirus, has arrived to Latin America in 2013. It became evident causing epidemics since 2015, first in Brazil and later in other countries in the region, such as Colombia, with a higher peak in 2016. The World Health Organization (WHO), based on cumulated evidence on its association with Guillain-Barre syndrome (GBS) and microcephaly and other birth defects (also the congenital Zika syndrome, CZS), declared for a period of almost a year, an international public health emergency. Epidemics in the region caused around 1 million cases with also additional complications beyond GBS and the CZS, which in patients with comorbidities lead to deaths. Among the events studied in the region, a number of cases with arboviral coinfections/codetection (dengue and chikungunya) were described and published beginning in Colombia and later in Brazil. In addition to that, cocirculation and still ongoing research on antibody-dependent enhancement (ADE) are challenges for physicians and public health authorities, given the implications for clinical manifestations and serological diagnosis in patients with previous exposition to other flaviviruses. We reviewed such aspects in this chapter.