Five years, 53,000 leads, and 6,000 subpoenas after those attacks, they still have no arrests.
Things are so cold, law enforcement officials tell CBS News, that barring the discovery of new evidence, the anthrax investigation could be declared a "Cold Case" and put in the inactive files.
So who did it? Former Attorney General John Ashcroft once singled out Dr. Steven Hatfill, a bioweapons specialist, as a "person of interest." But there have been no charges.
Former FBI counter-terrorism executive and now CBS News consultant Mike Rolince says no case has frustrated the FBI more.
"We now know that someone, or ones, can conduct an attack like this and for least the first five years, get away with it," Rolince says.
The FBI says it remains committed to solving the crime. In a written statement, Joseph Persichini, Jr., acting assistant director of the FBI's Washington field office said: "Today, the FBI's commitment to solving this case is undiminished ... While no arrests have been made, the dedicated investigators who have worked tirelessly on this case, day-in and day-out, continue to go the extra mile in pursuit of every lead."
The bureau never had more than scant physical evidence, like the envelopes the anthrax was mailed in, and the terse letters inside - "Death to America" read one - and the spores themselves. But they were never able to trace the anthrax back to the attacker.
"It's true that a vast majority of the investigation early on was figuring out the science," Rolince says.
Nor did the administration ever entirely figure out what to do in case of another such attack. Despite a $5.6 billion effort to stockpile vaccines, just a small amount is available. Only the Pentagon has enough on hand for the troops.
Homeland Security Secretary Michael Chertoff hints no one may ever be indicted.
"There are times that we may know a lot about a crime or an event that occurred, but we may not have the admissible evidence that we need to prove it in court," Chertoff says.
But the thinking among investigators is more stark: If we can't agree among ourselves who did it, they reason, how could we ever convince a jury?