Because of the increasing costs and complexity of vaccine design, the vaccine development pipeline is in need for a different, sustainable and cost-effective development model. Experimental medicine approaches such as the controlled infection of human volunteers can accelerate the development of novel vaccines through early proof-of-concept efficacy testing as well as by increasing the understanding of host-pathogen interaction in the human setting. As such, the development of human infection models has the potential to fill the gap between fundamental and preclinical vaccine research and generate knowledge that will foster the design and development of novel vaccines. More importantly, infection models may prove to be a method to reduce research and development costs and ensure that health care can be made accessible and affordable for populations worldwide, now and in years to come, including those affected by poverty. Continuing investment and scientific development of these models will increase insight in how and to what extent human models predict vaccine efficacy in downstream field trials, improve the yield of (immunological) correlates of protection and improve the ethical justification of added social value at the expense of exposing healthy volunteers to a risk. Because human models for malaria vaccine development are most advanced and have led to the development of attenuated parasite vaccination, ongoing investment into these vaccines is needed to ultimately ensure that the knowledge gained materializes into a vaccine amenable for global administration. As the field of malaria vaccines has taught us, transfer of human models to endemic areas can be challenging but is essential to unleash their full potential in the vaccine pipeline.