Jury selection has begun in Chicago in what is being billed as the biggest US organised crime trial in years.
The trial follows an FBI operation called Family Secrets
Joey "the Clown" Lombardo, who faces charges of racketeering, is alleged to have been the boss of a gang called the Chicago Outfit in the 1970s and 80s.
Four alleged associates are also going on trial. All five have pleaded not guilty. Investigators say at least 18 murders can be linked to the gang.
The judge has ordered an anonymous jury for the trial, due to take four months.
Mr Lombardo, 78, who was arrested early last year, reportedly earned his nickname "the Clown" because of his love of wisecracks.
The other defendants standing trial are James Marcello, 65, Frank Calabrese Senior, 70, Paul Schiro, 69 and former Chicago police officer Anthony Doyle, 62.
The FBI's investigation has been known as Operation Family Secrets because the man expected to be the prosecution's star witness, Nicholas Calabrese, is the brother of defendant Frank Calabrese.
Nicholas, who says he was a member of the Outfit for years, has pleaded guilty to several charges and has told prosecutors he has information on many killings allegedly carried out by the gang.
Among them is that of gangster Anthony "The Ant" Spilotro, who, with his brother Michael, was beaten to death and buried in a cornfield in Indiana.
In the 1995 Martin Scorsese film Casino the Joe Pesci character was based on Spilotro and he and his brother met a similar end.
The gang - which was once run by notorious gangster Al Capone - ran gambling, pornography and extortionate lending operations during the 1970s and 80s.
District Judge James Zagel decided to order an anonymous jury after the prosecution cited safety concerns.
Defence lawyers have objected on the grounds it will predispose the jurors to think the defendants must be dangerous.