Zenden was voted the best player in Holland in his fourth and final season at PSV Eindhoven, where he had been raised since 1993. He joined Barcelona in the 1998/99 season and won the Primera Liga title in his second campaign. He played 89 games in three years before being sold to Chelsea for £7.5 million prior to the 2001/02 season. Zenden struggled to become a regular at Chelsea and was loaned to Middlesbrough in the 2003/04 season. He scored Middlesbrough's winning goal against Bolton in the League Cup final from the penalty spot and played well enough to earn himself an additional one-year-contract sparking speculation that he might go to a bigger club if he continued to play well.
Zenden was voted Boro's supporters' Player of the Year in the 2004/05 season and as Liverpool came calling Zenden jumped on board, when his contract expired. Zenden's career at Liverpool never really took off even though Rafa put his faith in him in the 2006/07 Champions League season. Zenden only featured in seven Premier League matches in 2005/06, scoring twice, against West Ham in October and then against Portsmouth the following month when he headed in the rebound after Peter Crouch's penalty had been saved. The 2006/07 season was far more productive for "Bolo". He appeared in 30 matches, although eleven of those were as a substitute. He figured in several Champions League matches as Liverpool progressed to the Athens final and the last of his 47 appearances for Liverpool came in the final in the Greek capital.
The Dutchman joined Marseille on a two-year deal in July 2007 after his contract had expired at Liverpool. A quirk of fate brought him back to Merseyside much earlier than he could have expected with Marseille and Liverpool being paired in the same Champions League group. Zenden played at Anfield when Marseille won 1-0 in September but Liverpool gained their revenge in December when a convincing 4-0 away win ensured that they progressed to the knock-out stage of the competition leaving Marseille behind.
Zenden became a free agent when his two-year contract with Marseille expired in the summer of 2009 and Sunderland secured his services after he had impressed manager Steve Bruce during trials that took place in the October international break period. Zenden was a substitute in half of Sunderland's 38 Premier League matches in 2009/10, including both games against former club Liverpool. He scored twice, the second being an astonishing left-footed volley at the Stadium of Light against Tottenham in early-April. He signed a new one-year contract and during the 2010/11 season he appeared in 27 Premier League matches. Zenden retired on the final day of the season with the first goal in Sunderland's comfortable away win at already-relegated West Ham United. It was the sixty-fourth club goal of a senior career that started in 1993 and took him to four different European countries. He also represented his country, the Netherlands, 54 times between 1997 and 2004, scoring seven times. Zenden took on his first coaching role in November 2012 when he was appointed assistant to Chelsea' interim manager, Rafa Benítez, until the end of the 2012/13 season.
After leaving Chelsea at the same time as Benitez, Zenden returned to the country of his birth to become assistant to the head coach of Jong PSV, PSV Eindhoven's reserve team. By 2018 he had progressed to the first team set up, specialising in coaching forwards and wingers. He also works as a pundit for Dutch television and owns a health club in Maastricht.