The San Francisco Bay and delta system comprises the largest estuary along the Pacific Coast of the Americas and the largest remaining area for tidal-marsh vertebrates, yet tidal marshes have been dramatically altered since the middle of the 19th century. Although recent efforts to restore ecological functions are notable, numerous threats to both endemic and widespread marsh organisms, including habitat loss, are still present. The historic extent of wetlands in the estuary included 2,200 km2 of tidal marshes, of which only 21% remain, but these tidal marshes comprise >90% of all remaining tidal marshes in California. In this paper, we present the most prominent environmental threats to tidal-marsh vertebrates including habitat loss (fragmentation, reductions in available sediment, and sea-level rise), habitat deterioration (contaminants, water quality, and human disturbance), and competitive interactions (invasive species, predation, mosquito and other vector control, and disease). We discuss these threats in light of the hundreds of proposed and ongoing projects to restore wetlands in the estuary and suggest research needs to support future decisions on restoration planning.