Following her split with Macaulay, Rachel had a 12-episode guest-starring arc in 2007 on the Showtime series Californication. From 2009 to 2013, Rachel played the villain/demon Meg Masters on The CW series Supernatural. She took over the role of Meg Masters, which was originally played by Nicki Aycox.

Rachel has also appeared in Cold Case, Army Wives, Criminal Minds, and Sons of Anarchy.

The actress was diagnosed with Multiple Sclerosis (M.S.) in 2010. Following her diagnosis, she scaled back her acting career when walking became difficult. Despite being plagued with rumors of retirement, Rachel confirmed in 2019 that she wanted to grow her acting career again to represent disabilities in TV and film again. 

Rachel tweeted a photo of her auditioning in a wheelchair in November of 2019. She captioned the photo, "Feels right to mark this moment, first audition in my wheelchair. Big thanks to all of you who've encouraged me to go back to this acting thing." She then hashtagged "Representation Matters."

In addition to making her return to acting, Rachel is also now the executive director of the Random Acts organization, which is a non-profit that focuses on encouraging small moments of kindness. 

It is unclear if Rachel is in a relationship these days. She hasn't posted any photos with a potential love interest, but it wouldn't be too surprising if she decided to keep her personal life private following her highly publicized marriage to Macaulay Culkin.