This Special Issue comprises original research and reviews articles in the research area of computational biofluid dynamics, fluid–structure interaction, and acoustic phenomena of relevance to confined, unsteady, transitional, or turbulent fluid flow scenarios in the human body. The selected papers in this issue represent several trends in biofluid mechanics. The scope of the papers ranges from extending numerical methodology for handling the interaction between the flow and the vessel (fluid–structure interactions, FSI) to using computational tools to guide intervention in clinical situations.