Immunocompromised hosts, which encompass a diverse population of persons with malignancies, human immunodeficiency virus disease, solid organ, and hematologic transplants, autoimmune diseases, and primary immunodeficiencies, bear a significant burden of the morbidity and mortality due to coronavirus disease-2019 (COVID-19). Immunocompromised patients who develop COVID-19 have a more severe illness, higher hospitalization rates, and higher mortality rates than immunocompetent patients. There are no well-defined treatment strategies that are specific to immunocompromised patients and vaccines, monoclonal antibodies, and convalescent plasma are variably effective. This review focuses on the specific impact of COVID-19 in immunocompromised patients and the gaps in knowledge that require further study.