The estuaries and rivers of the western coast of Florida have been under intense study for some time to identify relationships between inflows, salinity, and natural resources. The molluscs have been shown to be especially sensitive to salinity in other parts of the world. The current study performed a meta-analysis of existing data sets of southwest Florida mollusc communities to identify salinity-mollusc relationships at regional scales. The mollusc species are controlled more by water rather than the sediment they live in or on. The most important variable correlated with mollusc communities was salinity, which is a proxy for freshwater inflow. Although total mollusc abundance was not a good indicator of inflow effects, certain indicator species characterized salinity zones in southwest Florida rivers. Corbicula fluminea (Müller, 1774), Rangia cuneata (Sowerby, 1831), and Neritina usnea (Roding, 1798) were the only common species that occurred in the oligohaline zone at salinities below 1 psu. Although C. fluminea was the best indicator of freshwater habitat, it is a non-native, invasive bivalve species. The bivalve R. cuneata is an indicator of mesohaline salinity zones with an estimated tolerance of up to 20 psu. The gastropod N. usnea is also common in fresh to brackish-water salinities. Polymesoda caroliniana (Bosc, 1801) was present at salinities between 1 and 20 psu, which span the oligohaline and mesohaline zones. Tagelus plebeius (Lightfoot, 1786), Crassostrea virginica (Gmelin, 1791), Mulinia lateralis (Say, 1822), Littoraria irrorata (Say, 1822), and Ischadium recurvum (Rafinesque, 1820) are also good indicators for polyhaline salinity zones. These salinity ranges can be used to predict changes in mollusc assemblages in response to alterations in salinity that result from actual or simulated changes in freshwater inflow.