The salinity gradient of estuaries plays a unique and fundamental role in structuring spatial patterns of physical properties, biota, and biogeochemical processes. We use variability along the salinity gradient of San Francisco Bay to illustrate some lessons about the diversity of spatial structures in estuaries and their variability over time. Spatial patterns of dissolved constituents (e.g., silicate) can be linear or nonlinear, depending on the relative importance of river-ocean mixing and internal sinks (diatom uptake). Particles have different spatial patterns because they accumulate in estuarine turbidity maxima formed by the combination of sinking and estuarine circulation. Some constituents have weak or no mean spatial structure along the salinity gradient, reflecting spatially distributed sources along the estuary (nitrate) or atmospheric exchanges that buffer spatial variability of ecosystem metabolism (dissolved oxygen). The density difference between freshwater and seawater establishes stratification in estuaries stronger than the thermal stratification of lakes and oceans. Stratification is strongest around the center of the salinity gradient and when river discharge is high. Spatial distributions of motile organisms are shaped by species-specific adaptations to different salinity ranges (shrimp) and by behavioral responses to environmental variability (northern anchovy). Estuarine spatial patterns change over time scales of events (intrusions of upwelled ocean water), seasons (river inflow), years (annual weather anomalies), and between eras separated by ecosystem disturbances (a species introduction). Each of these lessons is a piece in the puzzle of how estuarine ecosystems are structured and how they differ from the river and ocean ecosystems they bridge.