In "The Pants Alternative", it is revealed that when Leonard was young he had to give back a ribbon he won for an experiment seeing if lima beans grew better with classical music when his mother pointed out that his younger brother Michael had already done a lima-bean-growing experiment (do they grow worse with rock ‘n’ roll music?).
In "The Spock Resonance", Leonard reveals that Michael was mean to him, showing they don't have a good relationship.
In "The Explosion Implosion", Beverly mentions that of all her children's spouses, Penny is her favorite. This implies that Michael is now married, most likely to the New Jersey judge.
In "The Celebration Reverberation", Michael sends Leonard his Christmas letter and telling about all his accomplishments, including building a hospital in Rwanda. This causes Leonard to spiral about his own lack of accomplishments.
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 of his brother Michael and his sister having kids. 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
- Brother: Leonard Hofstadter
- Sister: Unnamed
- Uncle: Floyd
- Aunts: Edna, Nancy, Unnamed
- Cousins: Unnamed
- Grandfather: Unnamed
- Grandmother: Unnamed
- Wife: Unnamed
- Children: Unnamed
- Brother-in-law: Unnamed (via his own sister)
- Sister-in-law: Penny Hofstadter
- Nephews via his sister: Neil, Jeffrey, Scott, William, Richard
- Unborn niece or nephew via Leonard