The production of biodiesel from algae is optimized using bioethanol following four different transesterification paths: alkali, enzymatic, and heterogeneous catalysts and supercritical conditions. The reactors are modeled using response surface methodology based on experimental results from the literature. These reactor models are implemented together with short-cut methods for the other equipment (distillation columns, gravity separators, etc.) in order to recover the ethanol, separate the polar and nonpolar phases, and purify the glycerol and biodiesel produced to formulate the problem as a superstructure of alternatives. The aim is to simultaneously optimize and heat integrate the production of biodiesel using ethanol in terms of the reaction technology and the operating conditions. The optimal conditions in the reactors differ from the ones traditionally used because these results take the separation stages into account. In terms of the optimal process, the alkali catalyzed process is the most profitable, while the enzymatic one is also promising due to the lower consumption of energy and water, although it requires significant enzyme cost. (C) 2012 American Institute of Chemical Engineers AIChE J, 59: 834-844, 2013