This paper aims to identify challenges, and threats, and further explore opportunities for a new Biodiversity Friendly Fisheries Management Regime on the Issyk-Kul Lake in the Kyrgyz Republic. This lake is the second largest high-altitude lake in the world providing recreational and small-scale fishing activities as well as cage culture of introduced species. The populations of several indigenous species are seriously threatened, because many of the introduced species are potential predators. We examine the root causes for overfishing and relationships of alien and endemic fish species in Issyk-Kul Lake and give possible policy options that can help remediate or mitigate the biodiversity degradation. This analysis focuses on necessary legal modifications, institutional cooperation, the protection of selected endemic fish species, control of the alien species, the sustainable extension services and management of fish ponds. Fisheries co-management is one option to explore shared stewardship and empowering user groups on the lake. A comprehensive fisheries management plan is also needed, in addition to immediate action and further studies on the following wider aspects: water management/irrigation issues, water-quality assessment near cage cultures, sociocultural issues, resource inventory, and assessing fish biology and the lake ecosystem.