His best-known roles are the private detective Lucas on House, the deranged and sadistic kidnapper Jake in the HBO serial drama Six Feet Under, and Private Dancer on Scrubs, as well as Harry Houdini in Houdini & Doyle.

In 2000 he changed his surname to "Weston" as there was already a "Michael Rubinstein" in the Screen Actors Guild.

Weston is a good friend and former roommate of actor Zach Braff and has appeared in several features with him including Getting to Know You (1999), Garden State, Wish I Was Here and The Last Kiss, and in a multi-episode arc as a injured soldier on Braff's television show, Scrubs.

Weston has also appeared as Simon Marsden, Olivia Benson's half-brother on Law & Order: Special Victims Unit.

He made a guest appearance on White Collar[6] and Burn Notice (in which the main character, Michael Westen, has a name very similar to his).