Macrophages are the mononucleated cell which turns out into multinucleated cell. The process of multinucleation enhances the phagocytic action of the cell efficiently. The virulent virus at small doses while the temperate virus at high doses can cause cell fusion of both infected and uninfected cells producing multinucleation. There are two routes of cell–virus fusion namely endoplasmic and ectoplasmic. The present article aims to review the process of cell–virus fusion and its endoplasmic and ectoplasmic routes