Interdisciplinary research regarding the pesticide DDT has been ongoing since its synthesis in 1874, with thousands of publications appearing in the literature. The present review, on the 50th anniversary of the publication of Silent Spring by Rachel Carson, examines the state of knowledge regarding the presence and toxicity of DDT in two groups of top predators in the aquatic environment, mammals and birds. The objective is to outline the essential chemical information available on the fate of this most renowned persistent organic pollutant in the context of other lipophilic contaminants, as much in terms of the abiotic environment as for the tissue distribution of DDT derivatives. The facts associated with bioaccumulation and biotransformation as well as linkages to more and less known toxic effects are presented. The discussion highlights the better understanding derived from bird investigations initiated owing to the discovery of avian reproductive effects, in contrast to the challenges faced in research on marine mammals. Eggshell thinning was observed when there were fewer industrial chemicals in use, while in the 21st century the plethora of xenobiotics entering the food web increased exponentially. A discussion of sediment quality guidelines as well as tissue guidelines is presented to explain the derivation of threshold concentrations for toxic effects. Recommendations are made to continue research on environmental contaminants entering the food chain, covering more POP and relevant toxic endpoints. Developments to replace DDT are highlighted alongside the cautionary principle, plus the regulation program launched in Europe in 2002 that will be implemented in 2020 to replace harmful chemicals.