Evaporation dominates the removal of water from Lake Tanganyika, and therefore the oxygen isotope composition of lake water has become very positive in comparison to the waters entering the lake. The surface water in Lake Tanganyika has remained relatively unchanged over the last 30 years with a seasonal range of +3.2 to +3.5‰ VSMOW. Water from small rivers entering the lake seems to have a δ18O value between −3.5 and −4.0‰, based on scattered measurements. The two largest catchments emptying into the lake deliver water that has a δ18O value between these two extremes. This large contrast is the basis of a model presented here that attempts to reconstruct the history of runoff intensity based on the δ18O of carbonate shells from Lake Tanganyika cores. In order to use biogenic carbonates to monitor changes in the δ18O of mixing-zone water, however, the oxygen isotope fractionation between water and shell carbonate must be well understood. The relatively invariant environmental conditions of the lake allow us to constrain the fractionation of both oxygen and carbon isotope ratios. Although molluskan aragonitic shell δ18O values are in agreement with published mineral-water fractionations, ostracode calcite is ∼1.2‰ more positive than that of inorganic calcite precipitated under similar conditions. Ostracode shell δ18O data from two cores from central Lake Tanganyika suggest that runoff decreased in the first half of this millennium and has increased in the last century. This conclusion is poorly constrained, however, and much more work needs to be done on stable isotope variation in both the waters and carbonates of Lake Tanganyika. We also compared the δ13C of shells against predicted values based solely on the δ13C of lake water dissolved inorganic carbon (DIC). The ostracode Mecynocypria opaca is the only ostracode or mollusk that falls within the predicted range. This suggests that M. opaca has potential for reconstructing the carbon isotope ratio of DIC in Lake Tanganyika, and may be a useful tool in the study of the history of the lake’s productivity and carbon cycle.