2-Methoxyestradiol (2-ME) is a physiological metabolite of estrogen, which is excreted with the urine. In contrast to most estrogens, tumor growth-inhibiting effects were observed. Further studies have revealed that it may be an effective anticancer compound for many tumor types. Several different mechanisms have been attributed to 2-ME. Besides a strong antiangiogenic effect on endothelial cells and tumors, there is a tubulin-inhibiting mechanism, causing cells to arrest in the G2/ M phase of the cell cycle. In other tumors, p53-dependent and p53-independent mechanisms with induction of apoptosis have been shown. The number of different tumors examined for a growth-inhibiting effect is increasing, and new mechanisms are continuously described. In vivo studies in mice, rats, and dogs show no or very little toxicity, even at high doses. Here, we discuss the antitumor activity and their mechanisms. 2-ME appears to be a new anti-tumor compound with strong potential for clinical application.