Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is acquired by drinking water containing small crustacean copepods (water fleas) infected with D. medinensis larvae. Recent evidence suggests that the parasite also appears to be transmitted by eating fish or other aquatic animals. About 1 year after infection, the worm typically emerges through the skin on a lower limb of the host, causing pain and disability (1). No vaccine or medicine is available to prevent or treat dracunculiasis. Eradication relies on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, treatment of unsafe water with temephos (an organophosphate larvicide), and provision of safe drinking water (1,2). CDC began worldwide eradication efforts in October 1980, and in 1984 was designated by the World Health Organization (WHO) as the technical monitor of the Dracunculiasis Eradication Program (1). In 1986, with an estimated 3.5 million cases† occurring annually in 20 African and Asian countries§ (3), the World Health Assembly called for dracunculiasis elimination. The Guinea Worm Eradication Program (GWEP),¶ led by The Carter Center and supported by partners that include WHO, UNICEF, and CDC, began assisting ministries of health in countries with endemic disease. In 2021, a total of 15 human cases were identified and three were identified during January-June 2022. As of November 2022, dracunculiasis remained endemic in five countries (Angola, Chad, Ethiopia, Mali, and South Sudan); cases reported in Cameroon were likely imported from Chad. Eradication efforts in these countries are challenged by infection in animals, the COVID-19 pandemic, civil unrest, and insecurity. Animal infections, mostly in domestic dogs, some domestic cats, and in Ethiopia, a few baboons, have now surpassed human cases, with 863 reported animal infections in 2021 and 296 during January-June 2022. During the COVID-19 pandemic all national GWEPs remained fully operational, implementing precautions to ensure safety of program staff members and community members. In addition, the progress toward eradication and effectiveness of interventions were reviewed at the 2021 and 2022 annual meetings of GWEP program managers, and the 2021 meeting of WHO's International Commission for the Certification of Dracunculiasis Eradication. With only 15 human cases identified in 2021 and three during January-June 2022, program efforts appear to be closer to reaching the goal of eradication. However, dog infections and impeded access because of civil unrest and insecurity in Mali and South Sudan continue to be the greatest challenges for the program. This report describes progress during January 2021-June 2022 and updates previous reports (2,4).