In 1999, Kaczmarek was cast to play Lois in the sitcom Malcolm in the Middle, which premiered on January 9, 2000. TV Guide dubbed her role in the series as a "true breakout; a female Homer Simpson", and critics hailed her for her comic talents.. Fox.com Later, Kaczmarek would credit the show for bringing out her comedic side, saying, "[Before Malcolm] I couldn't even get auditions for comedies. I played very unfunny people."Malcolm in the Middle on TV.com
