It is well established that the immunological response to the seasonal trivalent influenza vaccine is attenuated in cancer patients. Furthermore, rates of seroprotection and seroconversion vary by malignancy type and are higher in patients with solid tumors, as compared either with those with hematologic malignancies or with allogeneic hematopoietic stem cell recipients. In 2009, a novel influenza strain prompted development of new vaccines and evaluation of alternative dosing strategies in an attempt to increase the rates of seroconversion in immunocompromised patients, further complicating this issue. Recent literature has demonstrated that the use of myeloablative chemotherapy regimens and biologics is correlated with decreased immunogenicity and response to influenza vaccines. Much debate still exists as to the optimal timing of influenza vaccination. Delaying vaccination from 1 week following standard chemotherapy up to 6 months following rituximab is increasingly supported by studies in this heterogeneous population.