He served as the deputy prime minister of Greece, responsible for the coordination of the Government Council for Foreign Affairs and Defense (KYSEA) and the new Economic & Social Policy Committee from 2009 to 2012.

[2][3][4] Pangalos was member of the left-wing Lambrakis Youth and, in 1964, a candidate for the Hellenic Parliament with the United Democratic Left (EDA).

In 1996 he was appointed Minister for Foreign Affairs and held the post until his resignation in 1999, in the aftermath of the scandal involving the leader of PKK, recognized as a terrorist organization by EU, Abdullah Öcalan: helped by individual members of the Greek intelligence agencies Öcalan entered Greece illegally and was then deported to Kenya, where he was captured by Turkish agents after leaving the Greek embassy at Nairobi.

They lack basic appreciation.”[5] Pangalos was briefly made Minister for Culture in 2000, an appointment which was widely criticized, in view of his previous statement that artists who had protested his handling of the Öcalan affair were kouradomanges (Greek: κουραδόμαγκες, "turd tough guys").

[7] A Greek experimental pop band named Plastic Flowers sampled his famous speech "mazi ta fagame" in their song "Sinking Ship / Vanished Crew".