This work deals with the optimization and enzyme reuse of lipase-catalyzed transesterification of low quality fish oil, as an environmentally friendly alternative for the biodiesel production. Three commercial immobilized enzymes, Lipozyme RM IM, Lipozyme TL IM and Novozym 435, which possess different specificity and resistance to alcohol inhibition, were employed using ethanol as acyl acceptor. For any of the lipases, the maximum yield was around 75 wt% after 8 h of reaction and 50 wt% of enzyme loading, but different ethanol to oil ratio were required. The response surface models obtained explained more than the 92% of the data, and were employed to reach optimal conditions. Maximum FAEE yield (82.91 wt%) was obtained using Novozym 435 and an excess of EtOH (1.82 g per g of oil). The reusability of the immobilized lipases was evaluated under the optimal conditions. It was found that Novozym 435 can be used for 10 consecutive cycles, with a maximum loss of activity of 16%, whereas Lipozyme RM IM and Lipozyme TL IM experienced more significant losses. An exponential model to predict and compare lipase behaviors towards several reusing cycles was proposed and validated towards the experimental data, thus simplifying the scaling up of processes.