Colorectal cancer is the second most common cause of death in cancer patients worldwide and difficult to treat, especially in advanced stages. Angiogenesis is a crucial process in colorectal cancer growth, development and dissemination, with significant implications for clinical management. Surgery followed by chemo- and radiotherapy is still the treatment of choice for most patients with colorectal cancer, although in advanced stages its results are frequently not satisfactory. However, inhibition of angiogenesis has been implicated as the potential, clinically effective, additional treatment strategy in advanced colorectal cancer, as antiangiogenic drugs allow controlling the tumor growth. Accordingly, the number of clinical trials confirmed, that anti-angiogenic therapy prolonged survival of colorectal cancer patients. However, the process of tumor angiogenesis and its regulation are highly complex. It depends on the balance between pro- and anti-angiogenic factors, secreted by endothelial, tumor and host-infiltrating cells. Therefore, development of efficient anti-cancer treatment targeting primarily tumor angiogenesis might be a major step in oncology.