(i) E2 binds to the cell surface via an unknown receptor and possibly glycosaminoglycans as attachment factors. (ii) CHIKV enters the cell through clathrin-mediated endocytosis. Acidification of endosomes leads to insertion of the fusion peptide in E1 into the endosomal membrane. (iii) Fusion of the viral envelope and endosomal membrane releases nucleocapsid into the cytosol. (iv) Disassembly of the nucleocapsid liberates positive-sense genomic RNA and nonstructural protein (nsP) translation occurs. (v) Four nsPs, together with genomic RNA and presumably host proteins, assemble at the plasma membrane (PM) and modify it to form viral replication compartments (spherules) containing viral dsRNA. nsP1–4 function as a replicase and localize to the spherule neck to generate genomic, antigenomic, and subgenomic vRNAs. (vi) Spherule internalization allows formation of large cytopathic vacuoles (CPV-1) that house multiple spherules. Spherules at the PM or within CPV-I are fully functional. (vii) Translation of subgenomic RNA produces the structural polyprotein, and capsid autoproteolysis releases free capsid into the cytoplasm. Translocation of E3-E2-6K-E1/E2-E2-TK polyproteins into the ER. E2/E1 are posttranslationally modified, transit the secretory system, and are deposited at the PM. (viii) Interaction of capsid and genomic RNA leads to formation of icosahedral nucleocapsids. (ix) Nucleocapsids assemble with E2/E1 at the PM, resulting in budding of mature progeny virions. (x) Later in infection, CPV-IIs form, containing hexagonal lattices of E2/E1 and are studded with nucleocapsids. (xi) CPV-IIs likely serve as transport vehicles and assembly sites for structural proteins, allowing formation of mature virions and egress.