On January 10, 2020, the first genomic sequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from a patient in Wuhan, China, was posted online. As of February 3, 2021, 468 000 sequences of SARS-CoV-2 from COVID-19 cases globally have been uploaded into publicly available databases, including more than 93 000 from individuals in the US. SARS-CoV-2, like other RNA viruses, constantly changes through mutation, with new variants occurring over time. Generally, when new variants become more common, they do so because of some selective advantage to the virus. Among the numerous SARS-CoV-2 variants that have been detected, only a very small proportion are of public health concern because they are more transmissible, cause more severe illness, or can elude the immune response that develops following infection and possibly from vaccination. In the recent months, 3 specific viral lineages reflecting variants of concern have emerged and merit close monitoring: B.1.1.7, B.1.351, and P.1.