Increasingly, more diseases are becoming vaccine preventable, but maintaining community and provider acceptance demands that the number of injections does not increase. Combination conjugate vaccines represent an inevitable and important advance. This paper reviews the efficacy and safety of combination conjugate vaccines, including immunological mechanisms underlying interactions among vaccine epitopes, the role of immunological memory, and correlates of immunity. Specific attention is given to the experience with combination vaccines against each of Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. The implications of these findings for different communities are discussed, key areas for further research identified and implications for post-licensure monitoring addressed.