One of the proposed benefits of targeted therapies is reduced toxicity and improved quality of life. The approval of a new broad family of molecularly targeted anticancer drugs represents one of the most significant recent advances in clinical oncology. The growth of solid tumors is dependent on their capacity to acquire a blood supply. Much effort has been directed towards the development of drugs that disrupt or normalize this process for cancer therapy. Some tumors also contain vasculogenic mimicry channels consisting of cancer cells and their extracellular matrix. In solid tumors, vasculogenic mimicry has been found to be strongly correlated with advanced-stage disease and poor outcome. In this review article, we summarize the clinical use of small molecules and therapeutic antibodies as angiogenesis inhibitors and their toxic side effects. We discuss vasculogenic mimicry of solid tumors and describe strategies for identifying putative tumor vascular targets. We end by discussing the future prospects for the clinical use of vascular targeting in treatment of cancer.