The coronavirus infectious disease (COVID-19) shows a remarkable symptomatic heterogeneity. Several risk factors including advanced age, previous illnesses and a compromised immune system contribute to an unfavorable outcome. In patients with hematologic malignancy, the immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is significantly reduced explaining why the mortality rate of hematologic patients hospitalized for a SARS-CoV-2 infection is about 34%. Active immunization is an essential pillar to prevent SARS-CoV-2 infections in patients with hematologic malignancy. However, the immune response to SARS-CoV-2 vaccines may be significantly impaired, as only half of patients with hematologic malignancy develop a measurable anti-viral antibody response. The subtype of hematologic malignancy and B-cell depleting treatment predict a poor immune response to vaccination. Recently, antiviral drugs and monoclonal antibodies for pre-exposure or post-exposure prophylaxis and for early treatment of COVID-19 have become available. These therapies should be offered to patients at high risk for severe COVID-19 and vaccine non-responder. Importantly, as the virus evolves, some therapies may lose their clinical efficacy against new variants. Therefore, the ongoing pandemic will remain a major challenge for patients with hematologic malignancy and their caregivers who need to constantly monitor the scientific progress in this area.