Reductionism has been the predominant research strategy of molecular and structural biology in the 20th century. According to Francis Crick (1966):«The ultimate aim of the modern movement in biology is to explain all of biology in terms of physics and chemistry». It is now realized that a complex biological system like the immune system possesses many emergent properties that are not present in the individual components of the system. Vaccination is firmly anchored in the biological realm and cannot be reduced to the level of chemistry. Immunological reductionism analyses the different components of the immune system separately (individual binding sites, T cell help, adjuvants, antibody affinity maturation, etc) and fails to explain how these constituents produce a synergy that leads to protective immunity. The use of monoclonal antibodies for dissecting neutralizing immune responses and designing appropriate vaccines has been particularly counterproductive. Future vaccine development will benefit if the current reductionist mindset is replaced by a more empirical and systems approach emphasizing clinical vaccine trials as the only effective strategy able to lead to vaccine discovery.