The development of the oxazaphosphorine cytostatics cyclophosphamide, ifosfamide, and trofosfamide was based on the idea of applying the transport form/active form principle to the highly reactive nitrogen mustard group. A critical analysis and synopsis of the available results and knowledge will include examination of the extent to which the hypotheses on which this concept is based have been confirmed by experimental and clinical findings: 1. Chemical synthesis succeeded in converting the reactive nitrogen mustard into an inactive transport form (latentiation). 2. The requirement that the transport form be enzymatically activated to the active form in the target organ (the cancer cell) has been achieved by a sequence of metabolic reactions. 3. The aim of considerably increasing the therapeutic index of alkylating agents has been achieved by the oxazaphosphorine cytostatics. The greater cancerotoxic selectivity is closely correlated with the cytotoxic specificity of their activated primary metabolites. 4. The cancerotoxic selectivity of oxazaphosphorines was further increased when mesna was introduced as a regional uroprotector. Mesna eliminates the risk of therapy-limiting urotoxic side effects of oxazaphosphorines. With mesna protection, these cytostatics can be given in higher doses with increased safety, and their therapeutic efficacy can be enhanced. 5. Stabilization of the primary oxazaphosphorines, e.g., by attaching 2-mercaptoethanesulfonic acid (mafosfamide), opens up new possibilities in preclinical investigations and in therapy, e.g., for the clonogenic stem cell assay, for in vitro purging in autologous bone marrow transplantation, for regional perfusion of tumors, and, in small doses, for immunomodulation, where appropriate, in conjunction with "biological response modifiers."