During the 1830s, the nucleolus was first described in eukaryotic cells (1-3). Later, an Italian pathologist, Giuseppe Pianese, noticed its importance as showing excessive volume in malignant cells (4). However, the nucleolus function remained unknown until the 1960s, when it was recognized as the site of ribosome biogenesis and the center for protein homeostasis (5-10). Homeostasis of proteins (proteostasis) is composed of a group of coordinated cellular functions which ensure protein synthesis, folding, and degradation. These mechanisms are needed throughout the lifespan of an organism to maintain a functional proteome. The nucleolus is a multifunctional organelle and the prominent intranuclear part of eukaryotic cells (11-14). Apart from conventional nucleolar function, the nucleolus is involved in three essential fields, including viral replication, stem cell biology, and cellular senescence. Knowing distinct functions of the nucleolus, it is understandable that many replicating viruses in the nucleus interact with readily accessible nucleolar materials. As small obligatory parasites, viruses use the host materials to replicate and divert some of the cellular mechanisms for their own life. They alter the function of host cells to create a situation that favors their replication and functional activities (15-18). Nucleoli go through important morphological and behavioral modifications due to various viral infections. When viruses enter cells, they replicate using nucleolar ribosomal activity and nucleolar DNA, leading to cellular damage. We review the current research providing new information on nucleolar function in viral infections, especially coronavirus disease 2019 (COVID-19).