Pseudomonas aeruginosa remains a serious pathogen for specific cohorts of patients where chronic infection is a poor prognostic indicator, such as those with cystic fibrosis, burn wounds or those who are immunocompromised. Significant disease burden is associated with a diverse spectrum of both nosocomial and community-acquired infections. To date, vaccines against P. aeruginosa have shown limited and often conflicting efficacy data, especially against heterologous strains, which are increasingly identified as co-colonisers of biofilms. While few studies have gone beyond Phase II clinical trials, a particular concern is the ability of P. aeruginosa to evade the immune system while provoking an immune response that contributes to the destructive nature of infection. Therefore, vaccine development needs to focus on preventing attachment and colonisation, as well as preventing conversion to a mucoid phenotype that is characteristic of the chronic condition that promotes pathology.