Dehydrosqualene and squalene synthase catalyze the redox neutral, and the reductive, head-to-head dimerization of farnesyl diphosphate, respectively. In each case the reaction is thought to proceed via an initial dissociation of farnesyl diphosphate to form an allylic carbocation-pyrophosphate ion pair. This manuscript describes the synthesis and testing of inhibitors in which a guanidinium or amidinium moiety is flanked by a phosphonylphosphinate group and a hydrocarbon tail. These functional groups bear a planar, delocalized, positive charge, and therefore should act as excellent mimics of an allylic carbocation. An inhibitor bearing a neutral urea moiety was also prepared as a control. The positively charged inhibitors acted as competitive inhibitors against Staphylococcus aureus dehydrosqualene synthase with Ki values in the low micromolar range. Surprisingly, the neutral urea inhibitor was the most potent of the three. Similar trends were seen with the first half reaction of human squalene synthase. One interpretation of these results is that the active sites of these enzymes do not directly stabilize the allylic carbocation via electrostatic or π-cation interactions. Instead, it is likely that the enzymes use tight binding to the pyrophosphate and lipid moieties to promote catalysis, and that electrostatic stabilization of the carbocation is provided by the bound pyrophosphate product. An alternate possibility is that these inhibitors cannot bind to the "ionization FPP-binding site" of the enzyme and only bind to the "non-ionizing FPP-binding site". In either case, all reported attempts to generate potent inhibitors with cationic FPP analogs have been unsuccessful to date.