She worked with Adi Shamir at the Weizmann Institute of Science, earning a master's degree there in 2001, and then moved to the Massachusetts Institute of Technology, where she completed her PhD in 2006 with Shafi Goldwasser as her doctoral advisor.

[2][3] She serves on the Scientific Advisory Board for the Institute for Computational and Experimental Research in Mathematics (ICERM).

[4] Kalai is known for co-inventing ring signatures, which has become a key component of numerous systems such as Cryptonote and Monero (cryptocurrency).

Subsequently, together with her advisor Shafi Goldwasser, she demonstrated an insecurity in the widely used Fiat–Shamir heuristic.

[5] Kalai was an invited speaker on mathematical aspects of computer science at the 2018 International Congress of Mathematicians.