While conjugate vaccines against typhoid fever have recently been recommended by the World Health Organization for deployment, the lack of a vaccine against paratyphoid, multidrug resistance and chronic carriage all present challenges for the elimination of enteric fever. In the past decade, the development of in vitro and human challenge models has resulted in major advances in our understanding of enteric fever pathogenesis. In this review, we summarise these advances, outlining mechanisms of host restriction, intestinal invasion, interactions with innate immunity and chronic carriage, and discuss how this knowledge may progress future vaccines and antimicrobials.