If he were to win the Democratic Party nomination from what could be a crowded field, Matthews would face off against the popular Republican Senator Arlen Specter. The 78 year old Specter was first elected to the Senate in 1980 and has confirmed he will seek reelection despite a recurrence of Hodgkin's Disease this year. Specter is one of the few remaining Northeast Republicans in Congress and his moderate stances often makes him a target of both the Left and Right.
A Matthews run would surely be entertaining, if only for the "did he really just say that?" moments, of which there would be plenty.