Book excerpt: The protection of water resources from deterioration in quality from pollution discharges has become one of the biggest challenge in sustainable water resources management in recent decades. In practice, most countries have adopted pollution control strategies and measures which are based on ‘end-of-pipe’ solutions, i.e. wastewater treatment plants and adjustments to the regulations, including taxes for wastewater discharges (Conventional Strategy). This approach involves very high costs, and it has in many cases has been a complete failure. The research described in this book contributes to the development of sustainable solutions for the previously outlined problem. It is based on the validation of the Three-Step Strategic Approach concept (3-SSA), which includes: 1) prevention or minimisation of waste production; 2) treatment aimed at recovery and reuse of waste components, and 3) polishing of remaining waste by stimulation of natural self-purification of receiving water body. The study on wastewater management in the Upper Cauca river basin (389 km), the second most important river in Colombia, shows overall positive effects of the 3-SSA, in comparison of Conventional Strategy. The Cost Benefit Analysis clearly favoured the 3-SSA, generating a major positive impact on the river water quality at lower cost compared to the Conventional Strategy.