In February 2020, the United States (US) and the Taliban signed a peace deal in Doha, Qatar which stipulated US troop withdrawal from Afghanistan by 1 May 2021. The Biden administration extended the deadline to 11 September 2021. The Doha agreement does not augur peace and stability in Afghanistan with the country predicted to suffer from protracted violence and even a civil war. The instability in Afghanistan will also cascade into the neighbourhood and beyond and lead to non-traditional threats/challenges. In the new millennium, while Russia, Iran and some Central Asian countries have borne the brunt of the narcotics trade emanating from Afghanistan, these countries along with India, China and Pakistan have also suffered from increase in terrorist attacks due to an unstable Afghanistan. Human migration has also negatively impacted the socio-economic and political milieu of Pakistan and Iran. This special section assesses the non-traditional security challenges/threats such as transnational Islamic fundamentalist terrorism, drugs/narcotics trade and human migration in the region and beyond posed by increasing instability and protracted violence in Afghanistan as a consequence of US withdrawal, and discusses the role (or the lack) of international and regional organizations and country initiatives in providing solutions to overcome or mitigate these problems.