This paper applies an ecosystem approach to analyse the livelihood of fishers dependent on the Old Brahmaputra River in Mymensingh, Bangladesh. Results suggest that the livelihood of fishers is increasingly threatened because of the fragile river ecosystem and poor livelihood assets. Most fishers face a wide range of vulnerability including shocks, trends and seasonality. This is because the ecosystem of the resource base on which their livelihood depends (i.e. the Old Brahmaputra River) has been degraded severely resulting in a significant decline in fish catch due to a combination of factors, such as over-fishing, use of destructive fishing gears, water pollution, siltation, rapid urbanisation and environmental degradation. We propose an adoption of the socio-ecological system with active community participation in the management of the resource base and collaboration amongst key stakeholders to produce positive livelihood outcomes for the fishers.