The expression "in silico", from which the album's title is derived, means performed on computer or via computer simulation. However group member Gareth McGrillen also commented on the way it plays upon Nirvana's well-known album title In Utero (which means born naturally or of the uterus) and thus carries extra shades of meaning related to being "born synthetically", thus explaining the album's cover design of a baby or fetus displayed inside a circular design representing a synthetic ovum.
Critical reception to the album has been mixed, with most of the polarization coming from Pendulum's shift from drum and bass to a more rock and pop-imbued electronic sound. Allmusic praised that "Pendulum is determined to heal the breach" between rock and electronica; however, The Guardian felt that the sound was "a little dated". Many fans of the first album have criticized In Silico for the change of genre; however, because of the album's popularity, and with singles being played on television music channels such as Kerrang!, Pendulum have managed to attract a new group of fans. Q Magazine named both lead single "Granite" and "Propane Nightmares" in the top 50 songs of the months in which they were released.
One lyric in "Mutiny" ("In through the rays of your reflection, we enter from a terminal connection") comes from "The Terminal" on Hold Your Colour. The songs "Granite" and "Showdown" are featured in the off-road video game Pure. "Granite", "9,000 Miles" and "The Tempest" are also featured in the video game Need for Speed: Undercover. "Showdown" also appears in the 2008 film Punisher: War Zone in addition to an episode of CSI: NY. Also, part of the song "Mutiny" appears in a Verizon Wireless commercial promoting the LG Dare, and "The Other Side" appears in an episode of EastEnders aired on 6 August 2010. The song "Propane Nightmares" was also used as the main theme for the WWE Pay-per view Cyber Sunday 2008 special and on the release trailer of Just Cause 2. "The Tempest" also appeared in TV spots for the film Ninja Assassin.
On 26 March 2008, Pendulum released a 12-minute mini-mix of the album – known as In Silico (El-Hornet Mini-Mix) – available only to those who are registered on their website. The track listing is as follows: