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The premise of this article is that climate effects on lakes can be quantified most effectively by the integration of process-oriented limnological studies with paleolimnological research, particularly when both disciplines operate within a common conceptual framework. To this end, the energy (E)–mass (m) flux framework (Em flux) is developed and applied to selected retrospective studies to demonstrate that climate variability regulates lake structure and function over diverse temporal and spatial scales through four main pathways: rapid direct transfer of E to the lake surface by irradiance, heat, and wind; slow indirect effects of E via changes in terrestrial development and subsequent m subsidies to lakes; direct influx of m as precipitation, particles, and solutes from the atmosphere; and indirect influx of water, suspended particles, and dissolved substances from the catchment. Sedimentary analyses are used to illustrate the unique effects of each pathway on lakes but suggest that interactions among mechanisms are complex and depend on the landscape position of lakes, catchment characteristics, the range of temporal variation of individual pathways, ontogenetic changes in lake basins, and the selective effects of humans on m transfers. In particular, preliminary synthesis suggests that m influx can overwhelm the direct effects of E transfer to lakes, especially when anthropogenic activities alter m subsidies from catchments.