Leonard's sister is only daughter of Alfred and Beverly Hofstadter, as well as the older sister of Leonard Hofstadter and Michael Hofstadter. She never appeared on the show, but has been mentioned a couple of times. It is known that she is a cutting-edge medical researcher working with gibbons to cure diabetes.
She is older than Leonard, as Leonard mentions in "The Cohabitation Formulation" that she is 38 years old and married, after Raj is mad at him for spending the night with his sister Priya and says in retaliation that he "shall have his way with Leonard's sister".
In "The Procreation Calculation", when Leonard suggests that he may be the last of the Hofstadter line (after learning Penny doesn't want kids), Sheldon reminds him that not only does Leonard's brother have kids, but his sister kept the Hofstadter name and has five sons: Neil, Jeffrey, Scott, William, and baby Richard. Realizing this, Leonard sees it doesn't matter if he has kids since his siblings' children will carry on the family line.
- Father: Alfred Hofstadter
- Mother: Beverly Hofstadter
- Brothers: Leonard Hofstadter, Michael Hofstadter
- Sons: Neil, Jeffrey, Scott, William, Richard
- Uncle: Floyd
- Aunts: Edna, Nancy, Unnamed
- Cousins: Unnamed
- Grandfather: Unnamed
- Grandmother: Unnamed
- Husband: Unnamed
- Sister-in-laws: Penny, Unnamed (via Michael)
- Unnamed nephews/nieces
- She is the only member of Leonard's family of whom her relationship with Leonard is unknown.
- However, as Leonard doesn't say anything bad of her they may get along.
- Having mentioned she is married in 2011 ("The Cohabitation Formulation"), Leonard refers to his sister as Dr. Hofstadter in 2012 ("The 43 Peculiarity"). It is quite usual for academics to keep their own surnames upon marriage though some wives still use their maiden names for professional reasons, especially if they were established before they were married.