The process of angiogenesis plays a pivotal role in embryogenesis, wound healing, and tumorigenesis through the growth of new blood vessels from pre-existing vasculature. Among the angiogenic factors recently identified as specific for vascular endothelium are the angiopoietins. In depth characterization of the angiopoietins has allowed investigators to better understand the molecular basis of blood vessel formation and vascular endothelial cell function. In this review, we describe angiopoietins and related family members, with particular emphasis on a recently identified protein known as angioarrestin. Our investigations clearly demonstrate that angioarrestin is an anti-angiogenic molecule. The effects of angioarrestin on tumor cell progression and specific aspects of the angiogenic cascade in in vitro models are further discussed.