On 25 November 2021, the world health organization listed Omicron as a newly arisen and the fifth variant of concern (VoC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome sequence of Omicron showed the utmost number of mutations compared to other known VoCs up to now, and it was regarded as the only SARS-CoV-2 variant with changes in the receptor-binding domain (RBD). However, the Omicron is still detectable via previous polymerase chain reaction (PCR) tests. Clinical presentation of the disease is identical to previous VoCs, however in vitro and in vivo studies revealed a higher transmission rate. The biggest obstacles posed by Omicron are the immune escape and reduction in vaccine effectiveness, as indicated by many simulations and real-world studies. Although the efficacy of the two-dose vaccinations is suboptimal for Omicron, preliminary studies have considered the injection of a booster shot is beneficial and can decrease the risk of severe disease. All these new features of Omicron warranted close investigation of this VoC as a new chapter in the pandemic, especially with emersion of subvariants BA.4 and BA.5. This review presents a conspectus of the current knowledge on the COVID-19 Omicron variant biological, clinical, and epidemiological changes.