Vaccines are the most efficient tools to battle infectious diseases, with an estimated prevention of 2–3 million deaths per year [1]. Vaccine development, however, is costly and challenging, especially when the target pathogen can be subdivided into serologically distinguishable types (serotypes) that individually cause disease. Broad protection against serotypes can be achieved with either polyvalent vaccines of mixed serotype-specific immunogens or by discovery and use of a good immunogen conserved among serotypes. The latter is preferable but technically elusive. The poliovirus vaccine (containing three poliovirus serotypes) was first used as a polyvalent vaccine, beginning with the establishment of the Global Polio Eradication Initiative in 1988, reducing poliomyelitis by 99%[2]. Polyvalency has been arguably more useful than using conserved immunogens to target multiple serotypes, and polyvalency has steadily advanced despite complexity and barriers to manufacturing. Here, we review challenges and developments in polyvalent vaccines.