The Yangtze River has been a source of life and prosperity for the Chinese people for centuries and is a habitat for a remarkable variety of aquatic species. But the river suffers from huge amounts of urban sewage, agricultural effluents, and industrial wastewater as well as ship navigation wastes along its course. With respect to the vast amounts of water and sediments discharged by the Yangtze River, it is reasonable to ask whether the pollution problem may be solved by simple dilution. This article reviews the past two decades of published research on organic pollutants in the Yangtze River and several adjacent water bodies connected to the main stream, according to a holistic approach. Organic pollutant levels and potential effects of water and sediments on wildlife and humans, measured in vitro, in vivo, and in situ, were critically reviewed. The contamination with organic pollutants, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and others, of water and sediment along the river was described. Especially Wuhan section and the Yangtze Estuary exhibited stronger pollution than other sections. Bioassays, displaying predominantly the endpoints mutagenicity and endocrine disruption, applied at sediments, drinking water, and surface water indicated a potential health risk in several areas. Aquatic organisms exhibited detectable concentrations of toxic compounds like PCBs, OCPs, PBDEs, and PFCs. Genotoxic effects could also be assessed in situ in fish. To summarize, it can be stated that dilution reduces the ecotoxicological risk in the Yangtze River, but does not eliminate it. Keeping in mind an approximately 14 times greater water discharge compared to the major European river Rhine, the absolute pollution mass transfer of the Yangtze River is of severe concern for the environmental quality of its estuary and the East China Sea. Based on the review, further research needs have been identified.