Born in Copenhagen, Rune Pedersen started his career off at clubs in his hometown. He played youth football with Hvidovre IF, before moving to Kjøbenhavns Boldklub, the reserve team of F.C. Copenhagen in the top-flight Danish Superliga championship. He got his first team debut for FCK in August 2000, when he replaced the injured Michael Stensgaard. He went on to win two Superliga championships with FCK, but never fully established himself as FCK's starting goalkeeper. He saw competition from a number of goalkeepers, including Swedish international goalkeeper Magnus Kihlstedt and Norwegian international goalkeeper Thomas Myhre. After two and a half years with FCK, he rejected a contract offer from the club in January 2003. He trained with English club Chelsea, but did not get a contract offer. Instead, he was sold to Italian club Modena F.C. in the Serie A championship. Pedersen only spent half a year with the club, before he was released in the summer 2003, after claiming he did not enjoy life in Italy. He trained with an English club again, this time Portsmouth, but finally moved back to Denmark to play for AGF Aarhus in August 2003. Initially a substitute for the three years younger Steffen Rasmussen, Pedersen made his AGF debut in April 2004, and was subsequently kept as starting goalkeeper. During the 2004-05 season, Rune Pedersen and five other players were fined for partying on a night where the team lost to Aalborg BK. He denied paying the fine, and even though the club later dropped the claim, Rune Pedersen was finished in AGF. He linked up with English side Nottingham Forest during their pre-season tour of Denmark in preparation for the 2005-06 season and whilst on trial won himself a two-year contract at the City Ground. After starting the season as first choice keeper the return to fitness of Paul Gerrard and the arrival of Russell Houlton loan from West Bromwich Albion relegated Pedersen to third choice goalkeeper. The departure of manager Gary Megson, Hoult returning to West Brom and further injury to Paul Gerrard presented Pedersen with another chance. Pedersen performed well in the eyes of many Forest fans and contributed to a resurgence in form which saw Forest climb to within two points of a play-off berth by the end of the season. The appointment of Colin Calderwood as the new manager of Nottingham Forest in June 2006 and the arrival of Southampton goalkeeper Paul Smith limited Rune to just a handful of appearances during the 2006-07 season. His contract was not renewed by the English club and consequently he became a free agent on 30 June 2007. Rune then signed with Danish Superliga club Lyngby BK. Lyngby were relegated following the Danish Superliga 2007-08 season, but Pedersen stayed with the club in the Danish 1st Division. On 29 August 2009 he was loaned to Superliga club Odense Boldklub for the rest of the year, but served as a back-up to Roy Carroll before returning to Lyngby in January 2010. Back at Lyngby, he helped the club finish second in the 2010 1st Division and gain promotion for the Superliga.