Farnesyltransferase enzyme (FTase) is currently one of the most fascinating targets in cancer research. Studies in other areas, namely in the fight against parasites and viruses, have also led to very promising results. However, in spite of the thrilling achievements in the development of farnesyltransferase inhibitors (FTIs) over the past few years, the farnesylation mechanism remains, to some degree, a mystery. This review tries to shed some light on this puzzling enzyme by analyzing seven key mechanistic dilemmas, based on recent studies that have dramatically changed the way this enzyme is currently perceived.