As the most frequently mutated oncogene in human cancers, the small GTPase Ras is a logical target for anticancer drug development. Ras proteins serve as molecular switches regulating many key signaling processes, including growth-promoting pathways critical for normal cell functions that go awry in cancer. How to interfere selectively and successfully in oncogenic Ras function has proved to be surprisingly vexing. The complexity and importance of controlling correct subcellular localization supports the development of inhibitors that disrupt specific aspects of Ras membrane binding. Here, we concentrate on assays and compounds relevant to inhibiting enzymes responsible for post-translational modifications required for full processing and correct localization of Ras proteins or their targets. Common modifications include farnesylation (by farnesyltransferase, FTase) or geranylgeranylation (GGTase I), proteolysis (Rce1) and carboxymethylation (Icmt), as well as palmitoylation (PATs) and phosphorylation (PKC). We discuss history, current status and prospects of inhibitors designed to block these steps of prenyl and postprenyl processing of Ras itself, or that appear to compete with oncogenic Ras (farnesyl-S-thiosalicylic acid, FTS) for key membrane binding sites that dictate its ability to transduce specific oncogenic signals. Recent patents focusing on GGTIs, Icmt and PATs, and on novel approaches to Ras inhibition, are emphasized.