The most universal abiotic influence is temperature, and thus, thermotolerance, adaptations and response to thermal variation, is a fundamental factor shaping evolution. Prokaryotic life may have an upper thermal limit near \(150^{\circ}C\); however, eukaryotic survival is limited to \(50^{\circ}C\) – the thermal maximum for sustained biosynthesis and homeostasis. My research focuses on understanding the physiological and biochemical factors that limit eukaryotic thermotolerance, by studying an organism near the upper limit of all eukaryotes: Paralvinella sulfincola. P. sulfincola, a hydrothermal vent polychaete, has the broadest known thermal range of any metazoan: \((5-48^{\circ}C)\). This species, along with the mesotolerant congener with Paralvinella palmiformis, is found at vents along the Juan de Fuca Ridge, Washington, USA. Making an ideal study system, both species are found in similar habitats, genetically comparable, and amenable to recovery and shipboard experimentation. Here, I present data from a series of high pressure in vivo experiments that investigate stress response to variations in temperature, pH, sulfide concentration, and duration. Field work was coupled with a suite of biomolecular techniques including pyrosequencing, comparative proteomics, enzyme assays, and quantitative PCR. From this research, the first to quantify global protein and antioxidant responses to temperature in an extremely thermotolerant eukaryote, three primary conclusions can be reached. 1) Pronounced thermal tolerance in P. sulfincola is likely enabled by its constitutive expression of heat shock proteins and limited by its ability to quickly and appropriately respond to the commensurate increase in oxidative stress. 2) Thermal tolerance limits are likely negatively affected by synergistic multistress effects. 3) Antioxidant gene expression response differs significantly between chronically and acutely stressed treatments, supporting the theory that oxidative stress is limiting in this system.