Natural killer (NK) cells are innate lymphocytes that participate in immune responses against viruses. NK cells contribute to host defense with their effector functions, either by directly restricting viral replication or by indirectly instructing anti-viral states in uninfected cells. In the case of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), robust activation of NK cells during acute infection and molecular recognition of infected cells in vitro are well studied. However, other aspects, such as the activation of specific sub-populations in severely ill patients or the unconventional cytotoxic arming of otherwise non-cytotoxic NK cell sub-populations, remain incompletely understood. Here, I review the thoroughly examined aspects of the NK cell response to SARS-CoV-2 and provide a brief overview of open questions surrounding this topic. Together, the existing data and the current unknowns will guide future studies and help navigate toward a better understanding of the host-pathogen interactions between NK cells and SARS-CoV-2.