This study aims to examine International Security Assistance Force or ISAF which has been implemented by NATO in Afghanistan. NATO, which founded during Cold War, was faced with post-Cold War international structure where everything is not the same anymore. Questions for NATO’s relevance was solved when NATO involved in humanitarian intervention in Balkan Peninsula during 1990s and took over ISAF from United Nations. Based on UN Security Council Resolution 1386, the establishment of ISAF was meant for providing security assistance for Afghan’s governments and helped to rebuild the country after US invasion of Afghanistan following terrorist attack in New York, known as 9/11 attack. This study uses qualitative method, and provides data taken from printed or e-books, journals, documents, papers, and websites. By using “theory of regime effectiveness” coined by Arild Underdal, this study reveals the factors of NATO ineffectiveness while implementing ISAF for a decade. Not only faced with malign problems during ISAF, NATO suffered from small capacity in problem solving which resulted in ISAF’s low effectiveness. In the end, any actions or policies conducted by ISAF participants cannot be separated from the view of participating countries in addressing various problems in Afghanistan.