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Zika virus (ZIKV) is an enveloped, mosquito-borne Flavivirus, which infects cells through clathrin-mediated endocytosis and fusion employing acidic endosomes. Cell entry is mostly mediated by the viral glycoprotein E, although incomplete particle maturation enables viral protein prM and anionic lipids present in the viral membrane to mediate this process. Incomplete proteolytic maturation results in a set of highly heterogeneous particles. These heterogeneous and dynamic infectious particles offer a variety of possible receptor interaction sites on their surfaces, thus contributing to the wide range of cells susceptible to ZIKV as well as to variation in tissue tropism. This review addresses recent advances in the understanding of ZIKV entry process into cells and put together fundamental questions about viral replication, maturation and host-cell interactions.