Vaccine development has played a hugely important role in combating infectious disease. Despite this success, there is still a great need for new vaccines and these are emerging far more slowly than we would wish. Despite the massive expansion in understanding of immune responses to infection, research is often hindered by a lack of understanding of the immune responses required specifically for protection, or by a lack of approved adjuvants and delivery systems to induce the required responses. In addition, the financial commitment required to license new vaccines is significant, and the more lucrative markets are often not those with the greatest need. In this review, we discuss many of the hurdles that new vaccines must overcome in order to reduce morbidity and mortality, and some of the initiatives that are being attempted to supply new vaccines to those that need them most.