The development of protein-polysaccharide conjugate vaccines has had a major impact on Haemophilus influenzae type b disease. The application of this technology to Neisseria meningitidis is also striking, particularly for serogroup C. However, significant challenges exist for the development of vaccines against non-typeable H. influenzae and against N. meningitidis serogroup B. Issues such as non-vaccine-strain replacement and correlates of protection need to be addressed as well as the longer-term implications of vaccination against what are essentially 'normal' microflora.