Mathijsen started his football career at SV VOAB in Goirle after he visited a training session of a friend as a young boy.

[citation needed] After finishing as runners-up in the Eredivisie in 2006, Mathijsen opted to transfer to German Bundesliga side Hamburger SV for €6 million, where he teamed up with fellow Dutchmen Rafael van der Vaart and Nigel de Jong.

[citation needed] Since his international debut, Mathijsen became a mainstay figure in the national team, especially after impressing with Hamburger SV.

Initially in danger of losing his spot to Wilfred Bouma, he followed it up with a decent enough performance at the Euro 2008 and remained first-choice.

[citation needed] Mathijsen was part of the Dutch team for the 2010 World Cup, managed by Bert van Marwijk.