Studying the interaction between fluid and structure is an essential step towards the understanding of many engineering and physical problems, from the flow instability of structures to the biolocomotion of insects, birds and fishes. The simulation of such problems is computationally challenging. This justifies the attempts to develop more sophisticated and more efficient numerical models of fluid-solid interactions. In this dissertation, we proposed numerical models both in potential flow and fully viscous flow for the interaction of immersed structure with a strongly unsteady flow. In particular we have developed efficient approaches to study two groups of problems, the flow interaction with skeleton-reinforced fish fins and flow interaction with highly flexible bluff bodies. Fins of bony fishes are characterized by a skeleton-reinforced membrane structure consisting of a soft collagen membrane strengthened by embedded flexible rays. Morphologically, each ray is connected to a group of muscles so that the fish can control the rotational motion of each ray individually, enabling multi-degree of freedom control over the fin motion and deformation. We have developed fluid-structure interaction models to simulate the kinematics and dynamic performance of a structurally idealized fin. The first method includes a boundary- element model of the fluid motion and a fully-nonlinear Euler-Bernoulli beam model of the embedded rays. In the second method, we use an improved immersed boundary approach. Using these models, we study thrust generation and propulsion efficiency of the fin at different combinations of parameters at both high-Re and intermediate-Re flow. Effects of kinematic as well as structural properties are examined. It has been illustrated that the fish's capacity to control the motion of each individual ray, as well as the anisotropic deformability of the fin determined by distribution of the rays (especially the detailed distribution of ray stiffness), is essential to high propulsion performance. We also note that this structural design is a recurring motif in nature. To understand flow-induced vibrations of deformable bluff objects, we study dynamics of a pressurized elastic ring within a uniform flow by using an immersed-boundary algorithm. The vibration of the flexible ring is decomposed into a pitching and flexible bending modes. Across the resonance region, nonlinear behavior of the ring is studied and the hydrodynamic loads are recorded. It is observed that within the resonance region, the lift force demonstrates a beating phenomenon reminiscent of findings from reduced models and low-degree -of-freedom systems