Vaccination is an important strategy for preventing infections in patients with hematologic malignancies. Hematopoietic cell transplant (HCT) recipients have diminished immunity against vaccine-preventable diseases after transplantation. Optimal timing for initiating immunization in the context of hematologic malignancies and after HCT, however, is not well defined, and data on the magnitude and duration of immune response to vaccines in this population are lacking. Factors such as degree of immunosuppression, administration of monoclonal antibodies, time after HCT, and presence or absence of chronic graft-versus-host disease may influence the immune response to vaccines and may pose safety concerns for certain vaccines, such as live-attenuated immunogens. Patients who received certain monoclonal antibodies (eg, rituximab, alemtuzumab) less than 6 months before vaccination have poorer immune responses to vaccines. New advancements in vaccine development are warranted to improve safety and immunogenicity of vaccination in immunocompromised patients.