Castellano became boss after Carlo Gambino's death in 1976. While many people wanted the position as boss, it is suspected that Gambino appointed Castellano as his successor because Castellano was married to Gambino's sister and Gambino was a man who believed that family should come first. But Gambino decided at the same time to make Aniello DelaCrosse his underboss, to prevent a street war from happening. After Gambino's death, DelaCrosse became Castellano's underboss.
It is said that Castellano tried to run the organization like a company, and his connections expanded to places as far away as Kuwait. Because of that, apparently he was not well liked among mafia bosses, but DelaCrosse supposedly wouldn't approve of an attempt on his life, so they could not try to harm him.
However, DelaCrosse died of lung cancer on December 2 of 1985, and apparently it was decided then that Castellano would have to go. On December 16, he and his driver were shot to death outside Sparks Steak House in Manhattan. It has always been rumored that John Gotti, Castellano's successor as head of the Gambino family, had Castellano killed. Sammy "The Bull" Gravano, a Gotti underboss, confirmed this when he entered into a plea bargain with the government in 1990