Semiconductor nanowires are promising building blocks for a diverse range of next generation electronic, photonic, and energy conversion devices. The physical properties of these materials, and nanostructures in general, are intimately connected to their structure, which must be controlled with atomic-level precision. Unfortunately, the accessible design space remains limited by a reliance on chemistries that were originally developed for 2-D thin film growth. The 3-D nature of nanowires requires new strategies with which to manipulate growth processes and engineer structure. This talk will provide an overview of our recent efforts to advance semiconductor nanowire complexity and function by expanding the available synthetic “toolkit.” Our experimental approach couples the real-time in-situ spectroscopic interrogation of nanowire chemistry with post-growth structural characterization. We connect nanowire crystal structure with the specific chemical bonds present during synthesis and, in doing so, provide a robust foundation from which to rationally achieve novel structural motifs. The role of hydrogen as the root cause of well-known phenomena in Si nanowire growth will be discussed in detail. We subsequently leverage this fundamental knowledge to generate new types of superstructures with user-defined periodicity.