In this review, the clinical pharmacology of high-dose doxorubicin is examined, and the pharmacokinetics of infusional doxorubicin at standard and high dose are compared. The data developed here, including recent clinical trials of high-dose infusional doxorubicin, demonstrate the safety and efficacy of doxorubicin administration at doses > or = 150 mg/m2 for patients with breast cancer and strongly suggest that the utility of this drug can be substantially increased with appropriate hematopoietic support.