Regime shifts –persistent changes in the structure and function of an ecosystem - are well-documented in many ecosystems but remain poorly understood in floodplain-river ecosystems. We apply a resilience perspective to large floodplain-river ecosystems by presenting three examples of plausible sets of alternate regimes that are relevant to natural resource management interests within the Upper Mississippi River and Illinois River. These alternate regimes include: 1) a clear water and abundant vegetation regime vs. a turbid water and sparse vegetation regime in lentic, off-channel areas, 2) a diverse native fish community regime vs. an invasive-dominated fish community regime, and 3) a regime characterized by a diverse and dynamic mosaic of floodplain vegetation types vs. one characterized as a persistent invasive wet meadow monoculture. For each set of potential alternate regimes, we synthesize known or hypothesized feedback mechanisms that reinforce regimes, controlling variables that drive regime transitions, and restoration pathways. The conceptual models presented here provide a framework for synthesizing our understanding of the dynamics of this ecosystem and are relevant to other large floodplain-river ecosystems that face similar human pressures across the world. The models are currently being used to prioritize future research, test hypotheses, and inform restoration and management on the Upper Mississippi River and Illinois River. Through sharing our approach, we provide a case study in which we document an important step in operationalizing resilience concepts for the management of natural resources.