In this issue of AJTMH, Roestenberg and colleagues report that healthy adults can be infected by the intradermal injection of aseptic, purified, vialed, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge).1 Because of the potential of this “challenge in a bottle” to standardize and dramatically expand the use of controlled human malaria infections (CHMI) for assessment of malaria vaccines, drugs, and diagnostics, and naturally acquired immunity and innate resistance to malaria, this approach to CHMI may well turn out to be one of the major achievements in malaria vaccine research and development of the past half-century.

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