Conventional cytotoxic chemotherapeutic drugs treat cancer either by direct killing or by inhibition of growth of cycling tumor cells. In addition, evidence suggests that cytotoxic agents may inhibit tumor growth through an antiangiogenic mechanism. "Metronomic" or frequent continuous administration of the same chemotherapeutic agents at lower doses may optimize their antiangiogenic properties. The effectiveness of metronomic chemotherapy regimens can be improved significantly by concurrent administration of antiangiogenic, endothelial-specific drugs. Preclinical studies have shown that integrating chemotherapy with antiangiogenic drugs can improve efficacy and circumvent the toxicity and drug resistance associated with standard or high-dose chemotherapy. Preliminary clinical studies have shown similar results. Further confirmation of this concept is required with randomized, controlled clinical trials.