Revised model for the mechanism of metronomic chemotherapy. Metronomic chemotherapy may directly affect tumor cells (brown and gray ovals), may cause direct endothelial cell death or growth inhibition (red ovals), or may decrease the mobilization or viability of bone marrow–derived CEPs, which contribute to the tumor vasculature (pink ovals). The study by Mancuso and colleagues in this issue suggests that the primary mechanism of action is via induction of endothelial cell apoptosis (green ovals). Adapted from Shaked et al³ with the authors' permission.