He had already portrayed Malcolm Reynolds in Firefly and would go on to reprise the role in the film Serenity. He also starred and sang in Joss Whedon's 2008 Internet musical "Dr. Horrible's Sing-Along Blog", along side Felicia Day. Although the two both appeared in the same episodes, neither appeared on screen together.
He currently plays the title role on the ABC drama Castle.
He was also named in the "People's Sexiest Men Alive" 2010 magazine.