Legal experts say that's often the case in criminal trials, but even more in a case with allegations that go back many years and little or no forensic evidence.
"In any case I've tried like this, the people who are the accusers have to come across exceedingly well," said veteran Harrisburg defence attorney Matt Gover. "And the defence has to demonstrate a theory to the jury that there's motive for them to lie or fabricate."
Jury selection in Sandusky's trial is to begin Tuesday morning in a central Pennsylvania courtroom.
Prosecutors allege Sandusky engaged in a range of sexual abuse of 10 boys over 15 years, charges he has repeatedly denied. Eight of those 10 alleged victims have been identified by investigators, and most, if not all, had been prepared to take the stand at Sandusky's preliminary hearing, which he waived at the last minute in mid-December.
Sandusky's lawyers have sought potentially damaging material from the alleged victims' pasts, including any history of making up stories, criminal arrests and psychological problems.
The defence will have their grand jury testimony to compare against whatever they say on the stand at trial, and have indicated they will try to show some of the accusers have collaborated, hoping to cash in through civil litigation.
"Joe Amendola has said during some of the hearings that the defence is going to turn on a claim that some, if not all, of these victims had motives to fabricate these allegations," said Wes Oliver, a law professor at Widener University School of Law in Pennsylvania.
John E.B. Myers, a law professor at the University of the Pacific in Sacramento and author or editor of eight books on child abuse, said the core issues in the Sandusky case are the same as many others.
"I think the overall issue is and always has been the child's credibility," he said, adding that the issue of memory will come into play, since the alleged victims are now adults.
Legal and scientific research also shows an interesting fact about juries in abuse cases, Myers said. "The one thing the literature is clear about is that women tend to believe children more than men do," he said.
The sex abuse case led Penn State's board of trustees to fire the legendary Joe Paterno as head football coach; leaders later said he hadn't done enough after he fielded an abuse allegation from a team assistant. The university's president was also ousted, and two administrators were charged with lying to a grand jury. At word of Paterno's firing, students rioted in the streets of State College, and Paterno's treatment remains a sore spot for many alumni and fans.
The expected testimony of Mike McQueary, an assistant coach who was a graduate assistant a decade ago when he says he witnessed what appeared to be Sandusky sexually assaulting a boy, could be a critical part of the prosecution's case.
Sandusky's lawyers will undoubtedly try to undercut his credibility through the use of his grand jury testimony, his testimony at a hearing in the related perjury case of the two university administrators, and statements about what he saw at the time and in the intervening years.
Prosecutors recently had to amend the charges against Sandusky to allege that the incident McQueary said he saw occurred in February 2001, not in March 2002 as previously indicated.
"One of the real questions, it seems to me, that the prosecution has to face is whether they put McQueary on" the stand, Oliver said. "If the jury is left with the impression that the independent witness is making up stuff, then why would people who stand to benefit from this not make stuff up?"
The attorney general's office will have to counter any contradictions or gaps in their witnesses' memories with a demonstration that they do recall the heart of the matter — the alleged criminal acts for which Sandusky will be on trial, said David A. Harris, a University of Pittsburgh law professor. The existence of multiple accusers should help prosecutors, he said.
"View it as silt in a riverbed," Harris said. "Their testimony will build up in layers. So even if there are individual problems with the testimony of particular witnesses, the picture will fill in as a whole."
Prosecutors, who unlike the defence have had access to the accusers during trial preparation, presumably know where any weaknesses in their testimony will be, and have developed a strategy to counter them, Harris said.
A. Charles Peruto Jr., a veteran defence attorney in Philadelphia, said Sandusky's lawyers can try to attack witnesses' credibility through cross-examination — looking to shoot holes their testimony — and by presenting evidence and testimony establishing witnesses had motives to lie.
"You're not going to have all eight (testify) in a credible manner," Peruto said. "I don't believe that there's going to be eight victims painting a picture. It's never that easy for the prosecution. Some of them get cold feet, some of them really mess up on details, and the way the details are driven home by the lawyers is going to make a difference."
Peruto said any conventional wisdom that the charges are a slam-dunk could work against the prosecution.
"You can never count a jury as a layup in any case," he said. "The more potential jurors read the case is ironclad for the prosecution, the more potential for rebellion."
Before they deliberate, jurors will probably get an instruction from the judge that tells them they can believe all, some or none of a given witness' testimony, Gover said. He said the existence of multiple alleged victims will be a powerful tool for the prosecution, recalling a trial in which he represented a defendant a year ago in a sexual abuse case with four accusers.
"When you have one victim on the stand crying, that's one thing," Gover said. "When you have four on the stand crying it's incredible. And it was devastating." His client was convicted.
Associated Press writers Kevin Begos in Pittsburgh and Michael Rubinkam in Allentown contributed to this report.