In keeping with the theme of this Edition of Burger's Medicinal Chemistry and Drug Discovery as a drug hunter's guide, six case histories of anti-infective drug discovery are presented. These were independently written by the project leaders or inventive authors and include (i) structure-based design of mannoside FimH bacterial lectin antagonists, (ii) phenotypic screen antimalarial clinical candidate (+)-SJ733, (iii) discovery and repurposing of Auranofin as a broad-spectrum anti-parasitic agent, (iv) discovery and development of antimalarial UCT943, a back-up candidate to MMV048, (v) medicinal chemistry of broad-spectrum aureobasidin-derived antifungals, and (vi) lessons learned advancing lantibiotics into preclinical and clinical development.