The song may be meant to describe the rigors of a musician's day-to-day life on the road, and its effect on his life as a whole, in connection with the themes of much of the album. But the lyric is more general:
The song starts off with an immediate, propulsive backbeat, with the melody carried by piano and throughout laced by David Lindley's distinctive pedal steel guitar work. Browne's vocal is emphatic, with strong backing vocal parts from Rosemary Butler and Doug Haywood; the arrangement overall conveys a headlong existence. The lyric's ages and years match up with Browne's, yet still the puzzled sentiment is universal:
"Running on Empty" was Browne's third-biggest hit single in his career (trailing only "Doctor My Eyes" and "Somebody's Baby"), reaching number 11 on the Billboard Hot 100 in spring 1978, and subsequently became his most-played song on classic rock radio formats. It became a staple of Browne's concerts, and whenever Bruce Springsteen has guested at such shows, they have shared vocals on "Running on Empty".
This song appeared in the 1994 film Forrest Gump, famously featured in the scene where Forrest was running across the United States. As a result, this song has become a popular addition to the iPod catalogues of many avid distance runners.
In August 2008, Browne sued presumptive Republican presidential nominee John McCain and the Republican National Committee for unauthorized use of "Running on Empty" in a television commercial mocking presumptive Democratic nominee Barack Obama's energy policy.