Lyrically, the band tends to address contemporary issues, such as sexuality, war, the environment, and the nature of God, humanity, and existence.

Entropia was described as "a well-needed breath of fresh air for a genre that was full of self-parody and self-indulgence," as it was "delivered with emotion, intelligence, integrity, passion, and poignancy".

[3] A Sea of Tranquility reviewer also defined the album as Pain of Salvation's most "eclectic"[4] release because of the varied song structures and arrangements.

This album was considered a darker and more complex effort than Entropia, with one reviewer noting that "in a world that demands instant gratification, those things for which one must labor to reach usually give greater satisfaction in the end.

[5] Another reviewer remarked that it was a more focused effort compared to its predecessor while also noting that it was a concept album which "contains several independent subtopics and, instead of directly telling a story, combines [interesting] lyrical themes in a very unusual and successful way."

Some of the concepts explored are the impact of nuclear waste on the environment and life, in particular at Lake Karachay in the former USSR; indigenous peoples' rights, displacement, and beliefs; and war and firearms.

After a short break to regroup, Pain of Salvation recorded their third album, The Perfect Element, Part I from March to July 2000.

"[8] The reviewer stated that Perfect Element I marked the beginning of a completely new era for the band and praised the bold experimentation in the songwriting and conceptual development.

In late 2001, Pain of Salvation recorded their fourth album, Remedy Lane, which was almost entirely written during a two-month period from August to September 2001 by Daniel Gildenlöw.

The shows were full productions replete with costumes, stage props, screen projections and the nine-part Orchestra of Eternity.

After the conclusion of the string of performances, the material was further refined by Daniel Gildenlöw prior to commencing the recording in February 2004.

"[12] BE included a song featuring samples culled from a special phone line that the band set up for fans to record their messages on "God's answering machine".

In 2004, Daniel Gildenlöw expressed his refusal to take part in the U.S. policy of fingerprinting all out-of-country visitors, as well as his contempt for the Bush administration.

On 21 February 2006, Kristoffer Gildenlöw, unable to attend rehearsals due to his relocation to the Netherlands, was asked to leave the band.

On 29 April 2007 the band announced that Johan Langell would depart at the end of the tour due to family commitments.

Late in 2008, Simon Andersson left the band to pursue his side projects and recover from the Scarsick tour.

[19] However, the project was delayed due to the bankruptcy of SPV, subsidiary InsideOut Music was acquired by Century Media, which allowed the band to finish the albums.

[21] The band performed during the first semi-final and qualified for the runners-up broadcast; however, they lost to Pernilla Wahlgren by a slim margin and did not progress to the finals.

[20]In late 2011 and early 2012, the band's lineup underwent significant turmoil, with Johan Hallgren and Fredrik Hermansson leaving at the end of the year,[23] touring bassist Daniel Karlsson joining the band on keyboards,[24] Gustaf Hielm returning on bass guitar, and Ragnar Zolberg joining on guitars.

During the same year, the band announced a new album, In the Passing Light of Day, based upon Gildenlöw's hospitalization with a life-threatening streptococcal infection.