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A hallmark of Nanoscience is the variety of wonderful new properties of matter when it is reduced to nanometer dimensions. Scientists and engineers around the world are working hard to exploit these properties in a broad range of applications, ranging from electronics to energy, as well as biology and medicine. One of the great challenges in this effort is controlling the organization of such small objects. We are presently exploring strategies which combine traditional lithographic patterning with new surface chemistries and biomolecular assembly to control the placement of individual molecules and electronically functional nanostructures over macroscopic dimensions. One direction we are pursuing involves lithographically directed DNA assembly. In this approach, we bind DNA molecules and DNA nanostructures to molecular-scale anchors on a surface in a way that retains the DNA shape and function. This provides a platform to study biomolecular interactions and to explore ways in which DNA can be used to organize the assembly of electronically and optically functional nanostructures, in order to take full advantage of their unique properties. We use a similar approach to create biomimetic surfaces which simulate specific physical properties of the extracellular matrix down to the single-molecule level. Developing an understanding of the factors required to elicit a given cellular response will yield insight into the functional complexes involved in specific cell behaviors and how these may be altered. Potential applications range from adoptive immunotherapy to the rational design of tissue scaffolds that can optimize healing without scarring.