The flavivirus are emerging and re-emerging arthropod-borne pathogens responsible for significant mortality and morbidity worldwide. The genus comprises more than 70 viruses, and despite genomic and structural similarities, infections by different flaviviruses result in different clinical presentations. In the absence of a safe and effective vaccine against these infections, the search for new strategies to inhibit viral infection is necessary. The life cycle of arboviruses begins with the entry process composed of multiple steps: attachment, internalization, endosomal escape and capsid uncoating. This mini-review describes factors and mechanisms involved in the viral entry as events required to take over the cellular machinery and host factors and cellular pathways commonly used by flaviviruses as possible approaches for developing broad-spectrum antiviral drugs.Copyright © 2021 Elsevier B.V. All rights reserved.