Worldwide, over 40,000 hematopoietic cell transplants (HCT) are carried out each year, with the majority of patients surviving long term. Owing to their new immune systems, these patients are susceptible to a variety of preventable infectious diseases. The 2009 influenza pandemic, the increase in pertussis and antibiotic-resistant pneumococcus, as well as recent outbreaks of measles and mumps in immunocompetent individuals further highlight the need for effective revaccination of HCT recipients. Post-transplant vaccine guidelines, including those published in 2009, recommend immunization of all patient groups at fixed times post-HCT. Although early vaccination to protect against vaccine-preventable diseases is desirable, there are still limited data on whether this approach is efficacious in patient groups whose immune recovery differs from recipients of an unmodified HLA-matched sibling transplant. In the absence of such data, prospective trials are needed to better define the optimal timing for immunizing recipients of alternative donors. Ideally, such trials should be designed to identify biological markers that will predict an optimal and durable vaccine response.