She is best known for providing the voice of GLaDOS, the primary antagonist of the Portal video game series, the Combine Overwatch AI in Half-Life 2, and the Administrator, the announcer in Team Fortress 2.

[5] In December 2011, McLain won the Spike Video Game Award in the category "Best Performance by a Human Female" for her voice acting as GLaDOS in Portal 2.

[6] In 2013, she lent her public support to gathering donations for the Kickstarter-funded LGBT gaming convention GaymerX.

[10] In 2021, McLain provided the voice of GLaDOS non-canonically, singing a verse in The Chalkeaters’ song "Count to Three" as a cameo.

[13] McLain now spends her days as a voice instructor, teaching at local community and children's theaters.