Life cycle analysis (LCA) is a trending methodology for evaluating environmental impacts associated with a product through its life cycle. This chapter presents the general model formulation for life cycle optimization, as well as systematic approaches to solve the resulting multi-objective mixed-integer nonlinear programming problems. We discuss the life cycle design of an algal biorefinery for the production of sustainable biofuels and profitable by-products. We review the existing articles for the simulation and optimization of the algal biorefinery processes. We show the importance of superstructure optimization, and introduce the technology alternatives that can be incorporated into an algal process superstructure. Subsequently, we show the optimization results of an algal biorefinery. We further summarize the challenges and possible directions for future life cycle algal biorefinery designs.