Angiogenesis is an indispensable mechanism involved in both physiological processes and various pathological conditions, such as inflammation, aberrant wound healing, tumor progression, and metastasis. Among many angiogenic stimulators and inhibitors, vascular endothelial growth factor (VEGF) is regarded as one of the most important members of the signaling protein family involved in blood vessel formation and maturation. The a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) proteins are a family of multifunctional proteinases. Such proteolytic enzymes are associated with various physiological processes, such as collagen maturation, organogenesis, angiogenesis, and reproduction. Importantly, deficiency or overexpression of certain ADAMTS proteinases has been shown to be directly involved in a number of serious diseases, including tumor progression and metastasis. This review explores in-depth the connections between ADAMTS proteinases as positive/negative mediators during angiogenesis and VEGF.