DC Comics continuity can be divided into four major timelines or “universes”: the Golden Age (1938 debut of Superman to early/mid 1950s); the Silver/Bronze Age (mid 1950s-1986); Post-Crisis (1986-2011); and the current “New 52″ universe.
Silver/Bronze Age

Post-Crisis: Matrix and Linda Danvers

Read more about Matrix and Linda Danvers.
Post-Crisis: Kara

Kara Zor-El was reintroduced in 2004 with a new origin story in SUPERMAN/BATMAN. She starred in the 2005-2011 SUPERGIRL series and played an active role in the Superfamily books and on a number of teams, until DC Comics relaunched their comic universe again with The New 52.
Read more about Post-Crisis Kara and her comics.
New 52

Supergirl currently stars in the rebooted 2011 Supergirl series and makes appearances in the New 52 Superfamily books.
TV and FILM

Read more about Supergirl in the DC Animated Universe and the SUPERGIRL film.
ALL AGES SUPERGIRL

Supergirl appears in a number of series that take place outside the main DC continuity. The miniseries Supergirl: Cosmic Adventures in the 8th Grade and the series Tiny Titans and its successor Superman Family Adventures have proved popular with their fun, accessible and iconic stories for all ages. Supergirl has also made appearances in the comics based on the DC Animated Universe.
Power Girl

Read more about Power Girl at Maid of Might’s sister site Power-Girl.org.
AME-COMI GIRLS
The digital-first series Ame-Comi Girls features an alternate universe of all-female heroes and villains. The character designs are based on a series of anime-influenced collectible figures. Recommended reading for Power Girl and for the chance to see a team book filled with reimagined female characters in every role, but not a good book for Supergirl. The series is action-packed and a lot of fun, and Power Girl plays a lead role starting with the Ame-Comi: Power Girl mini. However the often ridiculous costumes and gratuitous sexualization of the characters by some artists can be a real barrier, and Supergirl is almost immediately turned into Dark Supergirl and spends most of her small screen time incapacitated.
Read more about Ame-Comi Girls.