Angiogenesis is a highly controlled multistep process that allows the formation of a harmonious vascular network during embryonic development and in adults. In addition, tumor progression also involves a dedicated blood vessel supply to fuel the tumor mass, pirating physiological molecular and cellular mechanisms. However, tumor angiogenesis is a quite inefficient process, as perfusion is not optimal, vessel integrity is not guaranteed, and vessel network is irrationally organized. While fundamental molecular and cellular mechanisms have been the field of intense investigation, anticancer therapies have evolved with the possibility to target tumor angiogenesis. This review presents the different steps involved in the formation of normal and tumor angiogenesis, and how tumor vasculature abnormalities could contribute to tumorigenesis and conventional therapy failure.