In an increasingly globalised world, today's international challenges such as drug trafficking and climate change transcend national boundaries and require multi-level governance responses. Cities in particular, stand out as an essential governing unit with huge potentialin resolving some of 21st century's most pressing problems. With over half of the world's population living in urban areas today, cities are not only the sites where global problems are manifested, but also the sites where innovative policy solutions to these international challenges emerge. The recent explosion of the phenomenon of city-networks reflects intensifying city-to-city interactions in addressing global challenges. Under the framework of global governance, this thesis systematically and comprehensively analyses cities' concerted efforts in tackling global challenges in three major issue-domains, namely drug control, nuclear non-proliferation and disarmament ,and climate change. The dissertation argues that cities are an integral part of global governance, and that citynetworks yield most observable impact on global governance through diffusion of policy and technical expertise.