Long-term (1972-2005) data from Lake Geneva were analyzed to assess whether primary productivity (PP) has declined over years in response to phosphorus (P) reduction measures implemented in the 1970s, and to determine which factors were responsible for the response observed. The results revealed increases in PP and chlorophyll a, and a concomitant decrease in water transparency, which contrasts sharply with other large lakes undergoing nutrient loading controls. Our data revealed long-term increases in incident light, water temperature, water column stability (WCS), N:P ratios and Baccilariophyceae. Nitrogen, Daphnia and WCS, rather than P, were the major factors driving PP during the first part of the study (1972-1988). When P became the main nutrient driving PP (after 1988), the latter still increased, partly as a result of long-term increases in light and WCS, two factors not often considered when exploring climate influence on phytoplankton. Daphnia abundance decreased over time, and its coupling with phytoplankton changed from positive during the period of P abundance (1972-1988) to negative during the period of P scarcity (1989-2005), suggesting a change in the influence of Daphnia on phytoplankton and in food web structure. These data support the view that increases in climate-related factors may render the restoration of lakes more difficult, and showed that neglecting nitrogen, light and WCS, may hamper our understanding of lake responses to re-oligotrophication or lead to inappropriate management decisions, particularly in the context of global warming.