<p>Polychlorinated dibenzo-p-dioxins and dibenzofurans are highly toxic pollutants that persist in the environment, bioaccumulate, and pose serious risks to human health and ecosystems. Their widespread presence, linked to cancer, endocrine disruption, and immune system impairment, required the knowledge of their long-term effects and mitigation approaches, which has led to the investigation of their toxicities. This review provides an overview of research progress, challenges, state-of-the-art control technologies, and future perspectives in the field of toxicology. Toxicological studies emerged from Asia, Europe, and North America, with most studies from the USA. Epidemiological studies have linked exposure to PCDD/Fs with adverse health outcomes, such as cancer, developmental abnormalities, and immune system disorders. Various techniques have been developed among others to remediate PCDD/Fs, including electrokinetic treatment, thermal desorption, vitrification, and supercritical water for soil and sediment. Biological methods are frequently preferred because they are more economical and environmentally advantageous. Eliminating persistent organic pollutants pollution sources for soils as well as controlling, securing, and remediating polluted sites and reservoirs are urgently needed measures to limit exposure and ensure food safety. In terms of control technologies, significant progress has been made in the development of state-of-the-art approaches for mitigating PCDD/F contamination. The development of cheaper and faster analytical methods to accurately measure these compounds in environmental and biological matrices is encouraged.</p>