She was murdered by the Salem Strangler (Jake Kositchek) who thought she was Marlena.
It was a huge storyline because Samantha had been off the show for awhile. Viewers thought Marlena was dead and went nuts. There were groups who protested outside the studio gates, the phone lines were flooded with outraged fans, etc. Management even had Deidre Hall (Marlena) answer some of the calls from upset fans to tell them to keep watching, as there was a twist. Then the viewers and Salemites found out it was Samantha who had been killed.
Marlena went away for a few days (to the old lake house she and Don had) and Samantha was going to be in town for the weekend. Marlena left her apartment key for Samantha so she could stay in Marlena's apartment. Jake broke in and killed Samantha.
Contrary to popular belief, that was always the planned storyline. There are many who think the storyline was hastily rewritten to have the murder victim be Samantha instead of Marlena after the viewers went crazy. But Samantha died on Wednesday or Thursday and Marlena was revealed to be alive on a Monday or Tuesday the following week.