Semiconductor nanowires promise exciting advances in fields as diverse as optoelectronics, photonics, quantum computing, and energy harvesting. The physical properties of these materials, and nanostructures in general, are intimately connected to their structure, which must be controlled with atomic-level precision. This remains a challenging task in many systems and stems from an inadequate chemical understanding of common synthetic routes. This presentation will provide an overview of our recent efforts to bridge this knowledge gap. In particular, realtime in-situ infrared spectroscopy measurements coupled with post-growth electron microscopy demonstrate the important, and as of yet unrecognized, role of transient surface chemistry during vapor-liquid-solid nanowire growth. Our findings indicate that covalently bonded hydrogen atoms are directly responsible for the planar defects (e.g. twinning boundaries) and growth direction transitions (e.g. <111> vs. <112>) that are frequently observed for Si nanowires. We subsequently leverage this fundamental knowledge to create complex semiconductor superstructures via temporal modulation of growth chemistry. For example, the use of “molecular masks,” which either allow or prevent conformal epitaxy, enables the fabrication of diameter-modulated nanowires with user-defined periodicity. These and other newly developed synthetic strategies open a number of new avenues to rationally engineer the crystal structure and properties of nanoscale semiconductors.