The purpose of this review is to give an overview of strategies using natural and artificial substrates to present active biomolecules in the development of vascular structures. Two primary topics are discussed. The first is the replacement and augmentation of arteries using vascular grafts or stents. Second is the recruitment of microvasculature secondary to an ischemic event or for the purpose of developing perfused, large-volume tissue-engineered constructs. Significant overlap exists among these topics. The focus is therefore on specific drug delivery strategies with discussion of a number of emerging themes. Where applicable, results from clinical trials have been included. Early work in the field includes covalent and nonspecific immobilization of growth factors, while more recent work emphasizes biologically inspired control over localization and temporal presentation. Novel strategies for matrix-mediated release can deliver multiple growth factors and/or cells in a manner that mimics tissue development and healing. Challenges that remain within this field center on controlling reciprocal interactions among the three fundamental tissue engineering components of scaffolds, cells and signals.