While IV-VI materials were some of the first semiconductors ever studied, they have yet to reach widespread commercial application in optoelectronics. Unfortunately, the peculiar bonding and structure of the IV-VI rocksalts that provides them with unique electrical characteristics also makes them very difficult to incorporate on foreign substrates. The rocksalt IV-VIs, PbSe, PbTe, and SnTe, have a mixed-character bonding, which contributes to a curious band structure with a direct L-valley bandgap, low auger recombination, and high dielectric constant, all beneficial features for defect-tolerant optoelectronics, however achieving high structural quality has always been a problem. While the first PbSe and PbTe lasers were demonstrated almost 60 years ago, research on infrared materials has slowly shifted towards II-VIs, III-Vs, HgCdTe, and quantum cascade lasers, with many fundamental materials problems in the IV-VI family left unsolved. In this dissertation, I hope to address some of these questions, specifically related to material growth, and lay groundwork for further exploration of PbSe bonding, optical, and electronic properties on a more robust growth platform.As the field of epitaxial crystal growth inexorably advances, materials scientists are forced to tackle ever more challenging heteroepitaxial combinations. Beyond direct device applications, PbSe growth on III-V substrates is a compelling model system for understanding high energy interfaces incorporating changes in valency, interface charge, coordination, and lattice mismatch. This dissertation focuses on molecular beam epitaxy of PbSe on zincblende GaSb, InAs, and GaAs substrates. We find that on arsenic-terminated surfaces in both the (001) and (111) orientations, nucleation is controllable. By exposing a III-V surface to PbSe flux at a temperature above the PbSe re-evaporation temperature, the surface is converted to a better template for growth: subsequent low-temperature initiation of PbSe flux results in single-orientation films. The resulting heterovalent and heterocrystalline interfaces are mapped using high resolution scanning transmission electron microscopy, and possible mechanisms of interface formation are discussed, with emphasis on interfacial symmetry. As interfacial energetics have not yet allowed for layer-by-layer growth of PbSe on any foreign substrate, understanding and controlling island coalescence is the key to synthesizing high-quality PbSe films. By systematically varying lattice mismatch and comparing films grown in different orientations, different relaxation mechanisms can be activated and studied. We find PbSe island shape and coalescence behavior is a function of surface mismatch, chemistry, and local strain from extended defects. Extensive defect characterization using electron channeling contrast imaging and transmission techniques has allowed for direct characterization of these complex dislocation structures. Through these studies, we present multiple avenues towards high-quality PbSe film growth on III-V substrates. Fascinatingly, even in structurally defective PbSe and PbSnSe films, strong photoluminescence can be observed, speaking to the future of these materials as defect-tolerant infrared emitters and detectors.