Coastal areas are high-risk zones subject to the impacts of global climate change, with significant increases in the frequencies of extreme weather and storm events, and sea-level rise forecast by 2100. These physical processes are expected to alter estuaries, resulting in loss of intertidal wetlands and their component wildlife species. In particular, impacts to salt marshes and their wildlife will vary both temporally and spatially and may be irreversible and severe. Synergistic effects caused by combining stressors with anthropogenic land-use patterns could create areas of significant biodiversity loss and extinction, especially in urbanized estuaries that are already heavily degraded. In this paper, we discuss current ideas, challenges, and concerns regarding the maintenance of salt marshes and their resident wildlife in light of future climate conditions. We suggest that many salt marsh habitats are already impaired and are located where upslope transgression is restricted, resulting in reduction and loss of these habitats in the future. In addition, we conclude that increased inundation frequency and water depth will have negative impacts on the demography of small or isolated wildlife meta-populations as well as their community interactions. We illustrate our points with a case study on the Pacific Coast of North America at San Pablo Bay National Wildlife Refuge in California, an area that supports endangered wildlife species reliant on salt marshes for all aspects of their life histories.