In 1997, Cash was diagnosed with the neurodegenerative disease Shy-Drager syndrome. The diagnosis was later altered to autonomic neuropathy associated with diabetes. This illness forced Cash to curtail his touring. He was hospitalized in 1998 with severe pneumonia, which damaged his lungs. The albums American III: Solitary Man (2000) and American IV: The Man Comes Around (2002) contained Cash's response to his illness in the form of songs of a slightly more somber tone than the first two American albums. The video that was released for "Hurt", a cover of the song by Nine Inch Nails, fit Cash's view of his past and feelings of regret. The video for the song, from American IV, is now generally recognized as "his epitaph," and received particular critical and popular acclaim.
Cash died less than four months after his wife, on September 12, 2003, while hospitalized at Baptist Hospital in Nashville. He was buried next to his wife in Hendersonville Memory Gardens near his home in Hendersonville, Tennessee.