The second season begins with the introduction of Irina Derevko, Sydney's mother, who soon becomes a vital part of the series. Midway through the second season, the series underwent a "reboot" of sorts with Sydney successfully destroying SD-6 (after gathering valuable intelligence for tactical strikes from an airborne SD-6 server) and becoming a regular agent for the CIA, still in pursuit of former SD-6 leader Arvin Sloane, his associate Julian Sark, and the Rambaldi artifacts. Sydney's friends at SD-6, Marcus Dixon and Marshall Flinkman, are finally made aware of her dual identity and recruited into the CIA. Sydney also begins a romantic relationship with Vaughn, now that their relationship will not endanger them.
In the second half of the season, it is revealed that Francie Calfo, Sydney's best friend, was murdered and replaced by Allison Doren, a woman who was transfigured to look exactly like her. Allison was then in a position to spy on Sydney and Will. The end of the season saw Will critically injured and Sydney killing Allison, then falling unconscious. She awakens two years later in Hong Kong, unable to remember the two years that have passed. She soon learns that her friends and the CIA believed her to be dead, and Vaughn found a new love and is now married.