Death is considered by Christians to be a state of separation. In physical death, the spirit God has given to the body has been separated from the body. In spiritual death (called the "second death"), the soul is separated from God for all eternity, cast into the Lake of Fire. Jesus promises to believers that "those who overcome" through faith shall "not be hurt by the second death".

Throughout the Left Behind series, death commonly occurs, both at the hands of humans and as part of God's divine judgments against man. During the Tribulation, the world population is depleted to the point where only one-fourth of that population remained at the time of the Glorious Appearing, and a good deal of that remaining population was sent to the Lake of Fire at the "sheep and goats" judgment. The black horseman of the Seal Judgments is regarded a a personification of death.

Jesus and Nicolae Carpathia both died, and they were both resurrected. In Christian theology, Jesus' death and resurrection served to unite a believer to Christ's death so that one's body of sin can be done away with and that one would no longer be a slave to sin (Romans 6:5-10).

Those who are raptured and the believers during the Tribulation who managed to survive to the Glorious Appearing do not experience death. In the beginning of Left Behind, Irene Steele said to her husband Rayford, "Can you imagine, Rafe? … Jesus coming back to get us before we die!" At the end of the Millennium, after the incineration of Lucifer's army and Satan being sent into the abyss by Jesus, Rayford, a natural who had suffered slowed aging throughout the Millennium, was taken up to the new heavens and new earth and received a glorified body. Rayford felt and saw his body being stored to the physiological state that it was when he was thirty and had been given a gleaming white robe. He realized that this experience was similar to being raptured, and like his wife Irene, had not experienced death.

When Vicki Byrne was in the cave hideout of Cyrus's Mountain Militia, she had a discussion with Tanya Spivey where she was trying to reach out to her so that Tanya can acquire a saving faith in Jesus. Tanya believed in reincarnation due to the influence of her father, Cyrus Spivey, who believed in it, even though he does regard the Bible as a prophetic book. Vicki tries to disabuse her of reincarnation by citing Hebrews 9:27 that says that people die once and would then be judged.

After the Battle of Armageddon and defeat of the Unity Army, Jesus obliterated the physical forms of Ashtaroth, Baal, and Cankerworm who had bodies physically resembling Carpathia and wore dark suits, but without those bodies, they had reptilian forms. After they were obliterated, their remains were blood, skin, and scales that soon spontaneously combusted. Jesus said they were sentenced to "death", and there was no apparent spiritual form that remained to be condemned to the Lake of Fire. It seems that they had been annihilated, but the authors' theology does not subscribe to that.

Jesus also said to Leon Fortunato that death was too good for him before he was sentenced to the Lake of Fire.

At the end of the Millennium in Kingdom Come: The Final Victory, Death and Hell are both cast into the Lake of Fire at the Great White Throne judgment.

A minority of Christians interpret the Bible as teaching that the consciousness of the reprobate is ultimately annihilated. This annihilation may occur after they are resurrected again so that the reprobate can be judged by Jesus and come to the visceral realization that their denial of God's grace and refusal to repent of their sins resulted in them being denied of eternal life. (This position may imply soul sleep where souls, or at least those of the reprobate, would be unconscious before they are resurrected. The Left Behind series rejects the notion of soul sleep, at least for the saved, since the believers are portrayed to go to heaven after they die.) This position is called conditionalism, as the soul is not inherently immortal, but its immortality is conditional on God's grace. This stance can best be summarized by Romans 6:23.

For the wages of sin is death, but the gift of God is eternal life in Christ Jesus our Lord. [NIV]