Twenty years in the future, the world is ruled by vampires. Humans are in blood camps or hide from the bloodsuckers. One of the people in charge of the resistance is a young woman, Eve. Back in the present, it's some months after the end of the third season. Werewolf George is distraught because his wife, Nina, was killed--and he now has a baby-- Eve (Yes, who grows up to be that woman in the future). Of course, ghost Annie and werewolf Tom are helping with the kid. Vampire leader Griffin wants the baby dead, since according to vamp lore she'll lead his kind to destruction. Back in the future Eve kills herself--because as a ghost she can travel back to the past and tell Annie, George and Tom that they have to kill her as a baby in order to save the future.
In the next episode we're introduced to a vampire, werewolf and ghost that have been living together since 1955. The vampire Hal, is an old one and is thousands of years old. He's gone through long periods of being good and then going evil. Eve's ghost gets them to visit the other trio--and the old werewolf dies. And the ghost, Pearl, goes to the other side, leaving Hal behind. George gets killed--and Hal ends up living with Tom and Annie, so there's a completely different dynamic. The rest of the episodes have Hal dealing with his vampirism, Tom falling in love, Annie's powers increasing so that she can actually kill people by touch--and the vampire's plan to take over the Earth, which all hinges around the baby, Eve.
The season starts on a bit of a downer, with half the familiar characters dead or dying (and another major character makes her exit by the end of this season!) but Season Four is as good as the first. It literally puts new blood into the series. Highly recommended.