Several known genes are crucial for blood vessel growth and differentiation but the cues that shape the architecture of the vascular system are still unclear. On p. 5281,Isogai and colleagues examine the influence of blood flow dynamics on the patterning of blood vessels that develop in the vertebrate trunk. Following observations of zebrafish embryos that express green fluorescent protein throughout the vascular network, the authors describe a two-step process of angiogenesis in which primary sprouts emerge from the dorsal aorta and secondary sprouts arise from the posterior cardinal vein. The authors used silent heart mutant embryos, which have hearts that do not beat, to show that circulatory flow dynamics do not affect the development of the primary network and have little influence on the patterning of the secondary network. Importantly however, their results support the idea that circulatory flow does affect the patterning of interconnections between the primary and the secondary networks, consistent with the notion that the architecture of the vascular system is orchestrated by the interplay between `hard-wired'anatomy and flow dynamics.