Cyclophosphamide (CPM) was first synthesized in 1958 by Arnold and Bourseaux as part of a program to develop new anticancer agents with fewer side effects and greater efficacy than those in existence. There are now many reports of good response rates obtained with CPM in patients with both hematological and solid malignant conditions, and it has been widely accepted as an important component of multi-drug regimens. What remains to be proven, however, is whether CPM significantly improves survival expectancy when used either alone or in combination with other agents. It should be remembered that evidence of efficacy as a single agent in terms of response rate or even complete remission may not be translated into improved survival when that agent is incorporated into a multi-drug regimen. Before a chemotherapeutic agent is evaluated as part of a multi-drug regimen there should be adequate evidence of efficacy against the relevant tumor. In addition, the agent must be used at a dosage that has been established as adequate. Despite these safeguards, it is not necessarily true that the addition of the drug either alone or as part of a multi-drug regimen will improve survival. Further use of the agent alone or in combination would then be illogical, just as it would be to use agents that have been shown to be ineffective, or to use an agent at too low a dose. The purpose of this article is to review the accumulated experience with CPM in both adult and pediatric oncology in the treatment of solid tumors with the above considerations in mind.