Morphine combined blues and jazz elements with more traditional rock arrangements, giving the band a very unusual sound. Sandman's distinctive singing was described as a "deep, laid-back croon, and his songwriting featured a prominent beat influence. When asked by reporters to describe their music, the band created the label "low rock". One critical appraisal suggests that "Morphine immediately established a minimalist, low-end sound that could have easily become a gimmick: a 'power trio' not built around the sound of an electric guitar. Instead, with sly intelligence, Morphine expanded its offbeat vocabulary on each album.
Although Morphine was critically lauded throughout their career, it is difficult to measure their success commercially. In the United States the band was embraced and promoted by the indie rock community, including public and college radio stations and MTV's 120 Minutes (which the band once guest-hosted), but received little support from commercial rock radio and other music television programs. This limited their mainstream exposure and success in their home country, while internationally they enjoyed mainstream success and support, especially in Belgium, France and Australia.
Morphine recorded their debut album, Good, for the Boston-based Accurate/Distortion label in 1991. The album received positive reviews and established a small but devoted audience. The band subsequently signed to Rykodisc, which re-released Good under its own imprint.
Cure for Pain, released in 1993, increased the band's audience outside of New England, and singles like "Thursday" and "Buena" picked up some college radio play. During the recording of Cure for Pain, Deupree, who was suffering from health problems, was replaced by Billy Conway, who had previously played with Sandman in Treat Her Right. However, Deupree still played most of the percussion work heard on the album. Conway would stay on as a permanent member of Morphine while Deupree would later return to perform with the band, both in the studio and on the road. Morphine's final album credits both men and includes a photo of both drummers playing with the group simultaneously. After they completed Cure for Pain, the band toured the United States, Europe, Japan and Australia.
In 1994, "Sheila" and "In Spite of Me" were prominently featured on the soundtrack of the film Spanking the Monkey. The band returned to the studio in 1995 and produced Yes. In 1996, Morphine signed with DreamWorks Records.
DreamWorks released their major label debut, Like Swimming, the following year. It was a critical success, but did not break the band into the domestic mainstream as had been hoped. DreamWorks released a music video for the single "Early to Bed". Directed by Jamie Caliri and released in March 1997, the nightmarish yet humorous video became an instant favorite among fans and was later nominated for a Grammy award Also in 1997 B-Sides_and_Otherwise a collection of B-sides and live recordings was released.
The band's final studio album, The Night, was completed in early 1999. Around this time, Jerome Deupree once again begun performing live with the band again, making the group a four-piece. Deupree performs on ten out of eleven tracks on The Night, but is listed in the album's liner notes as a guest member.
On July 3, 1999, Sandman collapsed on the stage of the Nel Nome del Rock festival at the Giardini del Principe in Palestrina, Italy (near Rome). He was soon pronounced dead of a heart attack and Morphine immediately disbanded. The Night was released in 2000.
Later, singer and guitarist Laurie Sargent, a member of Orchestra Morphine and former vocalist for the band Face to Face, would join Colley and Conway in their first post-Morphine musical endeavour, Twinemen. Conway and Colley also officially formed the Hi-n-Dry independent record label and studio, converting Sandman's workspace into a commercial enterprise. The label's roster includes a number of their friends, colleagues and other Boston-area musicians. Orchestra Morphine still reunites on occasion but no longer tours.
In 2004, the Mark Sandman box set Sandbox was released by Hi-n-Dry. It contains two CDs and a DVD of previously unreleased material spanning Sandman's musical career. The DVD features clips from early Sandman shows, interviews from the Morphine tours, and various videos from other Sandman solo and group projects, such as Treat Her Right. However, the box set does not contain any Sandman material found in the Morphine catalogue, Morphine videos, or promotional material produced by Rykodisc or DreamWorks Records. Many believe this is the result of a less-than-cooperative relationship between the surviving members of the band and their former record labels, although both Colley and Conway contributed to the release of The Best of Morphine, released by Rykodisc in 2003.
Jerome Deupree continues to record with various jazz musicians and later became a member of the group Bourbon Princess.