[3] Dr. Tennore Ramesh joined ALS-TDF when his sister in law was diagnosed with ALS and setup the research facility and served as Chief Scientific Officer from inception until 2003.

ALS TDF constructed a biosafety level 2 lab in 2005, allowing for the expansion of "gene therapy and cell-based treatment pipelines.

[2] The next year, James Heywood resigned as president but joined the board and Sean F. Scott, who ALS runs in his family, replaced him.

[2][10] Steven Perrin, previously only chief scientific officer, was appointed CEO in 2009 following the death of Sean Scott.

[14] Various public figures, including Kelly Clarkson, Jimmy Kimmel, Shaquille O'Neal, Nancy O'Dell, Wolf Blitzer, the Miami Heat and Andy Cohen have participated in the challenge.

[17] In April 2021, Fernando Vieira, M.D., was appointed the chief executive officer of the ALS Therapy Development Institute by the board of directors.

The institute has raised and spent more than $100 million on research into effective treatments for ALS and practices open-source science.