Lake Victoria’s ecosystem has shown fundamental changes over its past recorded history in terms of nutrient loadings, productivity, faunal composition and fisheries. As yet, however, no attempt has been made to link the driving processes of eutrophication and fisheries to understand the feedback observed in fish stocks, food webs, exploitation patterns and trade. Single- and multi-species stock assessments, based on steady-state models with effort (and/or predation) as the only driver – still used in the region to advise on management – uniformly indicate overfished stocks of Nile perch that are in danger of collapse. These current views of overfishing are not validated by empirical observations. This chapter presents a holistic integrated ecosystem approach which combines a phenomenological analysis of key processes with a comprehensive set of simple indicators, covering physical, biological and human development, where directionality in time is made explicit to understand ongoing processes in the changing ecosystem. This new approach results in: (i) no signs of overfishing in any of the verifiable indicators; and (ii) biological production increasing over time together with effort and yield as a function of increased eutrophication. The results indicate that continued eutrophication presents a much graver risk to the resource base and thus livelihoods of Lake Victoria’s coastal populations than fishing pressure. Lake Victoria can serve as an interesting case study for the inherent risk of using traditional fish stock assessment in changing ecosystems, and for the development of holistic monitoring systems for ecosystem-based management.