The structure and function of alluvial Highly Dynamic River Systems (HDRS) are driven by highly variable hydrological disturbance regimes, and alternate between resistant, metastable states and resilient, transitional states. These are in turn subject to influences of feedback loops within hydrogeomorphic and biological processes. Here we consider how resistance and resilience largely determine HDRS ecosystem trajectories and how these characteristics can be modified by natural and anthropogenic processes. We review the mechanisms by which biodiversity can affect both resistance and resilience and introduce a conceptual framework that incorporates some unique HDRS characteristics. We suggest that resilient and resistant patterns frequently coexist in the active tract of these river systems, and that this coexistance promotes the return of metastable states after major disturbances. In contrast, highly resistant and poorly resilient patterns dominate at their external boundaries. The loss of these natural dynamics resulting from direct and indirect human impacts causes deviations to resistance and resilience patterns and therefore to HDRS trajectory. We propose that understanding the role of interactions between biological and physical processes that control resistance and resilience is crucial for system restoration and management.