The relationship between the tribrid-doppelgänger, Alexandria Gilbert and the vampire, Caroline Forbes.
They have been best friends since birth and have always been close, even despite Caroline's former jealousy of Alex. They are also best friends with Bonnie Bennett and Elena Gilbert, Alex's twin sister. In season one, Caroline started to date Alex's ex-boyfriend, Matt, but suspected he was still in love with Alex until it finally became clear that he had moved on. When Caroline became a vampire, she and Alex grew closer along with Elena while Bonnie temporarily ended her friendship with Caroline.
However, Alex and Caroline's relationship became tense temporarily when she came back from the summer with Klaus and Stefan. Soon after they're friendship was restored but then became tense once again when she went dark. After getting herself back, Alex, who was dealing with the return of the guilt and grief regarding the death of her brother, took some time before she was able to apologize to Caroline for her actions, but the two were able to rebuild their relationship over the summer on the phone while she was in New Orleans, pregnant with Klaus' child.
In Season Eight of The Vampire Diaries they've been closer than ever as their children along with Bonnie and Enzo's daughter, Lia have grown up together just like they did. Caroline also attended Stefan and Alex's wedding. The death of Alex's husband Caroline was their in person or on the phone talking to make sure she was not alone.