Patients receiving immunosuppressive therapies may be at increased risk for complications of vaccine preventable diseases, including influenza, varicella, and pneumococcus. However, studies suggest that patients with chronic illness may be inadequately immunized. In part, this is because of a paucity of formal vaccine studies in immune compromised populations. This review discusses the methods one uses to assess vaccine efficacy and provides an update on currently known data on the vaccine antibody responses in immune compromised hosts. Currently published studies suggest that influenza vaccine can be safely administered to patients with IBD on immunosuppression, and is effective in the majority of patients. Further formal studies with other inactivated vaccines (e.g., pneumococcal vaccine, meningitis vaccine) should be conducted. While some studies in immune compromised hosts suggest the live attenuated varicella vaccine can be given without adverse events, administration of this vaccine in patients on immunosuppression remains controversial.