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Nitrogen\u2010containing bisphosphonates, a current treatment for bone diseases, have been shown to block the growth of the <jats:italic>T. brucei<\/jats:italic> parasites by inhibiting farnesyl pyrophosphate synthase (FPPS); however, due to their poor pharmacokinetic properties, they are not well suited for antiparasitic therapy. Recently, an allosteric binding pocket was discovered on human FPPS, but its existence on trypanosomal FPPS was unclear. We applied NMR and X\u2010ray fragment screening to <jats:italic>T. brucei<\/jats:italic> FPPS and report herein on four fragments bound to this previously unknown allosteric site. Surprisingly, non\u2010bisphosphonate active\u2010site binders were also identified. Moreover, fragment screening revealed a number of additional binding sites. In an early structure\u2013activity relationship (SAR) study, an analogue of an active\u2010site binder was unexpectedly shown to bind to the allosteric site. Overlaying identified fragment binders of a parallel <jats:italic>T. cruzi<\/jats:italic> FPPS fragment screen with the <jats:italic>T. brucei<\/jats:italic> FPPS structure, and medicinal chemistry optimisation based on two binders revealed another example of fragment \u201cpocket hopping\u201d. 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