The field of angiogenesis received a huge boost in 2003 with the announcement of positive results in a phase III clinical trial using a vascular endothelial growth factor (VEGF)-blocking antibody for the treatment of cancer. Although the VEGF pathway has emerged as a central signaling pathway in normal and pathologic angiogenesis, several other pathways are also now recognized as playing essential roles. This review focuses on 2 specific areas. First, we summarize some of the work on newly discovered angiogenic signaling pathways by primarily describing the molecular biology of the pathways and the evidence for their involvement in vascular development. Second, we describe progress in therapeutic antiangiogenesis in cancer, particularly with agents that block the VEGF pathway.