Despite the "Best of the Box" album title, the demo version of "We Die Young" that appears here is not included on Music Bank and is therefore exclusive to this collection. In addition, "Iron Gland" is featured with the beginning drum found on the Dirt track "Dam That River". A "Best Buy Exclusive" issue of the CD included a bonus disc in a cardboard sleeve, with live versions of "Angry Chair" and "Man in the Box". The version of "What The Hell Have I" that appears here is the original version, not the remixed version that appears on Music Bank.
The album was certified platinum by the RIAA, and the revenue generated from the album was used to fund the Music Bank box set. The album has received mainly positive reviews, with critics praising the compilations inclusion of rare material, along with the band's hits. Allmusic staff writer Steve Huey gave the album a four star rating writing "The package is not unattractive, since nearly all the hits are present in some form; also included are the new song "Get Born Again" and the better of the group's two contributions to the Last Action Hero soundtrack, "What the Hell Have I." Bill Adams of Ground Control Magazine, reviewing Alice in Chains Discography wrote "To its credit, Nothing Safe is a solid compilation of odds, ends, live tracks, studio cuts, soundtrack appearances and rarities, which serves its purpose for giving 'in-passing' fans a pretty enjoyable set".