Farnesyl pyrophosphate (FPP) is a central intermediate in multiple biosynthetic pathways, including those that lead to steroids, prenylated proteins, higher isoprenoids, and dolichols. Agents that inhibit the formation of FPP necessarily have an impact on all of these processes, but analogues may have differing impacts on the enzymes that employ this pyrophosphate as a substrate. Through preparation of phosphonate, bisphosphonate, and pyrophosphate analogues of FPP we have sought inhibitors of protein prenylation and higher isoprenoid synthesis, as well as alternate substrates for farnesyl:protein transferase. Synthesis of a variety of phosphorus containing compounds, and some studies on their biological activity, will be described in this presentation.