Regeneration reuse water systems can obviously reduce freshwater usage and wastewater discharge, and avoid unexpected accumulation of contaminants. Appropriate process decomposition strategies can help to further reduce freshwater usage and avoid recycling. In this paper, the effect of different process decomposition strategies on saving freshwater usage is analyzed on the concentration-mass load diagram. For multiple-contaminant water systems, the approach for the determination of interim concentrations for concentration decomposition is explored. Three sequential mathematical models and related optimization procedure to optimize regeneration reuse water networks are proposed. The propose approach is general and can be utilized for the synthesis of single/multiple-contaminant regeneration reuse water networks. Three illustrated case studies demonstrate the applicability and effectiveness of the proposed approach, (C) 2011 Elsevier B.V. All rights reserved.