The former head of Colombia's Cali cocaine cartel, made his first U.S. court appearance Monday, after being extradited from Colombia late last week.  The case could turn out to be the biggest drug conspiracy trial in U.S. history.  

Gilberto Rodriguez Orejuela, 65, made a brief appearance in federal court in Miami, where he faced charges of conspiracy to smuggle and distribute tons of cocaine, and obstruction of justice, by murdering witnesses. 

The charges are at the center of a 14-year investigation into his family's multi-billion dollar drug smuggling and money laundering business.  U.S. authorities also want to seize $2.1 billion, an amount they say Rodriguez Orejuela and his brother, Miguel earned from cocaine smuggling.  

Gilberto Rodriguez Orejuela was extradited to the U.S. from a prison in Colombia where he and his brother had been serving time on drug trafficking charges.  Because Colombian law prohibits the extradition of drug suspects accused of crimes committed before 1997, both men are charged with continuing to run their cocaine cartel from jail between 1999 and 2002.  Miguel Rodriguez Orejuela and three other senior cartel members are expected to be extradited to the U.S. soon.

U.S. Attorney Marcos Jimenez, whose office will try the case, says it marks a milestone in the fight against illegal drugs.

"When it comes to the world of narcotics traffickers and the prosecution of drug cases, it simply does not get any bigger than this," he said.  "This is a very significant moment in our nation's war on drugs.  This is the biggest extradition that our office, and probably the entire country, has ever had.  Certainly in narcotics cases, and maybe in any case." 

Federal authorities say the Rodriguez Orejuela brothers were at one time responsible for 80 percent of the global cocaine supply. They say Gilberto Rodriguez Orejuela faces a maximum sentence of life in prison if convicted. 

In an interview with a Colombian radio station just days before he was extradited, Rodriguez Orejuela admitted to being involved in the drug trade before 1995, but said he is innocent of the charges in the Miami indictment. His Miami attorney Jose Quinon says it will be a difficult trial.

"We know from prior cases of this magnitude that it is virtually impossible to get a fair trial, because when an individual of this magnitude comes over, the publicity that he brings with him really undercuts any chances of getting a fair trial.  Having said that one has to hope that out there, there will be a jury that will at least listen to us and hopefully take seriously what we have to say," he said.

About 100 individuals have already been arrested, tried and convicted in the 14-year-old operation against the Cali cartel.  Under the government of Colombian President Alvaro Uribe cooperation between U.S. and Colombian law enforcement authorities has improved dramatically in recent years.