Limnologists have long recognized that one of the goals of their discipline is to increase its predictive capability. In recent years, the role of prediction in applied ecology escalated, mainly due to man’s increased ability to change the biosphere. Such alterations often came with unplanned and noticeably negative side effects mushrooming from lack of proper attention to long-term consequences. Regression analysis of common limnological parameters has been successfully applied to develop predictive models relating the variability of limnological parameters to specific key causes. These approaches, though, are biased by the requirement of a priori cause-relation assumption, oftentimes difficult to find in the complex, nonlinear relationships entangling ecological data. A set of quantitative tools that can help addressing current environmental challenges avoiding such restrictions is currently being researched and developed within the framework of ecological informatics. One of these approaches attempting to model the relationship between a set of inputs and known outputs, is based on genetic algorithms and programming (GP). This stochastic optimization tool is based on the process of evolution in natural systems and was inspired by a direct analogy to sexual reproduction and Charles Darwin’s principle of natural selection. GP works through genetic algorithms that use selection and recombination operators to generate a population of equations. Thanks to a 25-years long time-series of regular limnological data, the deep, large, oligotrophic Lake Maggiore (Northern Italy) is the ideal case study to test the predictive ability of GP. Testing of GP on the multi-year data series of this lake has allowed us to verify the forecasting efficacy of the models emerging from GP application. In addition, this non-deterministic approach leads to the discovery of non-obvious relationships between variables and enabled the formulation of new stochastic models.