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Destroy All Humans! (2020):    • Destroy All Humans! - Playthrough  
Destroy All Humans! (2005):    • Destroy All Humans! - Playthrough  

Destroy All Humans! is an open world action-adventure video game developed by Black Forest Games and published by THQ Nordic. It is the fifth installment in the Destroy All Humans! franchise, and a remake of the 2005 original game. This remake is the first entry in the franchise since Path of the Furon (2008).

The game was released on Microsoft Windows, PlayStation 4, and Xbox One on July 28, 2020 and later on Stadia December 8. The game received mixed reviews upon release. A Nintendo Switch port was announced on April 8, 2021 and is set to release on June 29, 2021.

The game is played from a third-person perspective. The player controls Cryptosporidium 137 ("Crypto" for short), an alien who arrives on Earth in 1950s America to harvest human DNA. Crypto is equipped with a vast arsenal of alien weapons such as the Zap-O-Matic and Anal Probe, to defeat enemies. He also has superhuman skills such as psychokinetic powers and the ability to disguise himself as humans. Crypto can use a jetpack to quickly navigate the environment. He can also command the flying saucer, which is equipped with a death ray to kill opponents. Players can perform movements such as gliding and dashing, and they can chain actions together such as shooting enemies while levitating them. The game introduces the Focus Mode, which allows players to lock onto other enemies. Crypto is protected by a shield, which informs players the direction of hostile attacks. The game features six sandbox locations which can be explored freely. Each location offers unique challenges for players to complete.

A team of 60 people in Black Forest Games served as the game's developer. The original game's dialogue and humor remained intact, though the team enhanced them by updating the character models and cutscenes and introducing motion capture. Instead of re-recording the lines, the team used the audio from the original game and improved its quality for the remake. The game also includes a mission named "Lost Mission of Area 42" that was scrapped during the development of the original game. Black Forest considered developing the remake as a "natural continuation" of their work after finishing the development of Fade to Silence as they learned more about utilizing the technology and designing large, open areas.

THQ Nordic acquired the intellectual property rights from THQ in 2013. In 2017, the firm reaffirmed that the company realized the demand for a new game in the series and added that they were exploring options to revitalize the franchise. The game was officially announced in June 2019. An extended gameplay demo was launched at E3 2019. It was released for Microsoft Windows, PlayStation 4, Xbox One and Stadia.

Destroy All Humans! received "mixed or average" reviews, according to review aggregator Metacritic. Sales on the game have exceeded THQ Nordic's expectations.