But the band reunited again in 2015 for an extensive North American tour.
The legendary guitarist was known to have health problems that would interfere with his work for years.
He underwent hip surgery in 1999 and had part of his tongue removed in 2000 after being diagnosed with cancer, likely because of heavy smoking.
Although he was declared cancer-free following the surgery, the American tabloid news site TMZ reported earlier this year that he had been going to Germany for throat cancer treatment.
His drug abuse and heavy drinking contributed to his 2007 divorce from TV actress Valerie Bertinelli after 16 years of marriage.
"I was an alcoholic, and I needed alcohol to function," he said in a 2015 interview with Billboard magazine.
'Guitars weeping everywhere'
"I didn't drink to party. Alcohol and cocaine were private things to me. I would use them for work. The blow keeps you awake and the alcohol lowers your inhibitions. I'm sure there were musical things I would not have attempted were I not in that mental state."
Tributes from some of the biggest names in the music world poured in Tuesday following news of his death.