Injection drug use is a prevalent global phenomenon; one not bound by a country's level of development or geographical location. Injection drug users (IDUs) are at high risk for a variety of parenterally acquired and transmitted infections. Licensed vaccines are available for some of these infectious diseases, such as tetanus, influenza, and hepatitis A and B viruses; however, there have been conflicting reports as to their immunogenicity in IDUs. We summarise the lessons learned from studies evaluating the immunogenicity of vaccination strategies in IDUs. A common theme across these diseases is that although there is a tendency towards decreased antibody responses after immunisation, there is no conclusive evidence linking these observations to a decrease in clinical protection from infection. There is a clear need for definitive studies of vaccination strategies in IDUs; however, a synthesis of the available published evidence suggests that immunisation does result in effective clinical protection from disease in this population. The inclusion of IDUs as a high-risk study population in future trials evaluating HIV and hepatitis C virus vaccines will help to assess the immunogenicity of candidate vaccines against parenteral exposure, and also to evaluate the efficacy of candidates as promising antigens become available.