Cyclophosphamide (CP) is one of the oldest anticancer drugs, but one that is also highly effective by today’s standards. The theoretical idea for the development of CP was to administer a nontoxic prodrug that liberates in tumor tissue nitrogen mustard which damages DNA by alkylation. At the time, when CP was developed, it was believed that enzymes that catalyze splitting of phosphorus–nitrogen bonds (phosphoamidases) were preferentially found in tumor tissue [1,2]. This was the basis for the development of pro drugs from which alkylating nitrogen mustard should be split off in the target tissue “tumor”. Of the substances synthesized based on this theoretical requirement, CP proved to be the most effective in animal experiments. The theoretical concept was wrong, but the result was a very effective anticancer drug.