Vascular gas embolism—bubble entry into the blood circulation - is pervasive in medicine, including over 340,000 cardiac surgery patients in the U.S. annually. The gas–liquid interface interacts directly with constituents in blood, including cells and proteins, and with the endothelial cells lining blood vessels to provoke a variety of undesired biological reactions. Surfactant therapy, a potential preventative approach, is based on fluid dynamics and transport mechanics. Herein we review literature relevant to the understanding the key gas–liquid interface interactions inciting injury at the molecular, organelle, cellular, and tissue levels. These include clot formation, cellular activation, and adhesion events. We review the fluid physics and transport dynamics of surfactant-based interventions to reduce tissue injury from gas embolism. In particular, we focus on experimental research and computational and numerical approaches involving how surface-active chemical-based intervention. This is based on surfactant competition with blood-borne or cell surface-borne macromolecules for surface occupancy of gas–liquid interfaces to alter cellular mechanics, mechanosensing, and signaling coupled to fluid stress exposures occurring in gas embolism. We include a new analytical approach for which an asymptotic solution to the Navier–Stokes equations coupled to the convection-diffusion interaction for a soluble surfactant provides additional insight regarding surfactant transport with a bubble in non-Newtonian fluid.