The Lain multimedia franchise was designed from the start to span anime, video game and manga simultaneously, with the video game's scenario actually written first even though the anime was released first.

Producer Yasuyuki Ueda described creating Lain partly as 'a sort of cultural war against American culture', hoping Japanese and American audiences would interpret the show differently; he was disappointed to find American viewers largely shared the Japanese interpretation.

The English spelling of the heroine's name was undecided for a long time, with both 'lain' and 'rain' tested in sketches by character designer Yoshitoshi Abe before 'lain' was finally chosen around March 1997.

Character designer Yoshitoshi Abe filled 11 sketchbooks of 100 pages each while developing Lain's look together with producer Ueda and writer Konaka, deliberately avoiding designs that could be reduced to a simple line or symbol.

Lain's asymmetrical left forelock was specifically requested by producer Ueda to reflect her unstable, disconcerting nature and was designed as a mystical symbol meant to block voices and spirits from being heard by her left ear.

Lain's bear pajamas were requested by character animation director Takahiro Kishida; writer Chiaki Konaka initially opposed the idea, but director Nakamura convinced him it could work as a symbolic shield for Lain's confrontations with her family.

The series was made during a transitional period for TV anime digital production: digital cut scenes were created on consumer-grade PCs and Macs (rather than expensive SGI workstations) and stored on 2GB (later 4GB) hard drives, then composited with telecine-transferred cel film footage.

For the 2010 Blu-ray restoration, the original 1998 standard-definition material stored on Betacam had to be manually restored to high definition, a very difficult process since some source material had already been discarded or was in poor condition.

The series is filled with Apple computer references because most of the creative staff were Mac enthusiasts: each episode's title is announced using Apple's PlainTalk speech synthesizer voice 'Whisper', and the NAVI computers run a fictional 'Copland OS Enterprise' referencing Apple's actual cancelled OS project.

An iMac and the 'Think Different' advertising slogan appear briefly during a montage as an unsolicited addition by the graphics team, who were also Mac enthusiasts; the video game's tagline 'Close the world, Open the nExt' references NeXT, the company later bought by Apple.

Writer Chiaki J. Konaka denied any influence from Neon Genesis Evangelion, stating he had not even watched it until after finishing the fourth episode of Lain; his stated influences instead include Godard, The Exorcist, and Dan Curtis's House of Dark Shadows.

The characters Alice, Julie and Reika were carried over by Konaka from his earlier work Alice in Cyberland, itself inspired by Alice in Wonderland; Konaka said he was surprised how closely Alice's character ended up resembling the original Wonderland character as the series developed.

The opening theme 'Duvet' was performed by Bôa with lyrics by Jasmine Rodgers, while the ending theme 'Tooi Sakebi' was composed and performed by Rei 'Chabo' Yasuda.

The anime won the Excellence Prize in the Animation Division at the 2nd Japan Media Arts Festival in 1998 for its philosophical questioning of contemporary life.

Unlike the anime, the PlayStation game received little attention at launch and was criticized for its lack of gameplay, awkward interface, and long loading times, though its CG graphics and background art were praised; a fan English translation was completed and released as a PDF in 2014, and an unofficial WebGL browser port called 'lainTSX' appeared in 2021, sparking renewed interest in the game.