Angiogenesis is a physiologic process characterized by the sprouting of a new blood vessel from a pre-existing one. In mammalians the angiogenesis process is dormant, except for few physiological conditions such as wound healing and ovulation. In healthy individuals angiogenesis is finely tuned by pro- and anti-angiogenic factors. The shift from this equilibrium, under pathological conditions (pathological angiogenesis) is associated with several human diseases of high social impact. An efficient angiogenesis also requires that angiogenic factors cooperate with microenvironment derived co-factors, including metals. In this Perspective we describe the bioinorganic aspects of angiogenesis which contribute to a better understanding of the molecular mechanisms and regulation of angiogenesis. In particular, the role of metals, especially copper, metalloproteinases, and the current status on the imaging of angiogenesis targeting VEGF or VEGF receptors will be discussed.