Since ancient times, humans have been using nature to fulfill their needs, and in this process, they have been shaping the environment and changing the face of the earth. Human activities in more recent times have started harming urban riverine ecosystems across the globe, and these impacts are far more severe in developing countries. Extreme levels of pollution and degradation of rivers flowing through the densely populated cities in the developing world are nothing new. River Mithi, which runs through Mumbai, the most populated city in India, has turned into a model example of a degraded urban riverine ecosystem. This study explores the ramifications of human activities on River Mithi of Mumbai, using satellite imageries, journal articles, reports, and websites, along with personal observations on the study area. We find that the Mithi River is severely polluted by human activities, which include encroachment by slums, industrial waste, and poor sanitation, thereby practically turning this river into an open sewer. Despite attempts toward restoration, not much success has been achieved. Therefore, restoring it would require a comprehensive strategy. Measures that could be part of such a strategy have been suggested in this chapter, such as using environmentally friendly drainage technologies, cooperation between various stakeholders, and efficient flood management plans that could facilitate the cleaning of the Mithi River to a pollution-free ecosystem.