The paper presents a methodology for the integrated treatment of biorefinery effluents using a systems engineering approach. The methodology uses generic bipartite graphs to integrate biorefinery units and to compose superstructures. The graph representation accounts for biorefinery processes, waste treatment technologies, raw materials, intermediates, and products. Graphs are applied in conjunction with allocation maps that link treatment technologies with biorefinery liquid, solid, and gas streams. The superstructures integrate process technologies, include options for central and distributed treatment, and are applied both in grassroots and retrofit applications. The mathematical optimization requires the solution of mixed-integer nonlinear programming models, and the methodology is illustrated by using a real-life lignocellulosic biorefinery featuring 49 streams and 22 treatment technologies (6 for liquids, 4 for solids, 7 for gas pollutants, 2 for water reuse, and 2 for catalyst regeneration). When first generation plants are retrofitted into second generation biorefineries, systems integration proves capable to identify cost-effective alternatives that restrict cost. Results generally demonstrate that integration is exceptionally important, often leading to significant savings and cost reductions, even able to turn treatment costs into profits.