California’s native inland fish fauna is in steep decline, a pattern which is reflected in the status of fishes native to streams flowing into the San Francisco Estuary and in the estuary itself. Climate change will further reduce the distribution and abundance of these mostly endemic fishes and expand the distribution and abundance of alien fish species. The decline and likely extinction of many native fishes reflects dramatic shifts in the state’s aquatic ecosystems; shifts which are being accelerated by climate change. Fishes requiring cold water, such as salmon and trout, will especially suffer from climate change impacts of warmer water and reduced summer flows. Additionally, desirable species living in the San Francisco Estuary and the lower reaches of its streams will have to contend with the effects of rising sea level along with changes in flows and temperature. This paper: (1) briefly describes the environment of California and its fish fauna, (2) summarizes the projected general effects of climate change on its aquatic environments, (3) discusses likely interactions of climate with other stressors of fish populations, (4) describes possible effects on fishes of the San Francisco Estuary, and (5) suggests elements of a conservation strategy for the native fish fauna, focusing on the San Francisco Estuary