- The original run of the show ran from 1988 to 2002. By this point all of these cases are at least 20 years old, most of them 30 years older or more. As time goes on, witnesses and evidence will become even harder to come by and interest in solving them will fade as law enforcement agencies accept the likelihood that no new information will ever be found to help solve them. The loved ones of murdered and missing persons will die never knowing what happened to the one they lost, lost families will never be reunited, and criminals who committed heinous crimes have gotten away with them, and even if they were arrested and put in prison or executed on a separate charge, they will never face accountability for the crimes no one knows they did. Then one realizes that more unsolved mysteries are happening every day, and like these cases, decades from now some of them will still be unsolved.
- The Lost Loves section had some really big ones. A good example is a case where a former Ill Girl was searching for her hospital roommate to fulfill a promise they made: since the latter girl was rendered unable to have kids in adulthood, the former promised that when she herself had children, she would share them with her friend and name her first girl after her. Nikki Wade-Crowder gave birth to a daughter and was able to find Charita Harding-Buckner, who stood godmother to Charita Kennedy Crowder, aged three.
- A straight version would be the story of Dolores Ford and Irene Love, who grew up in the same 1950s neighborhood and were close like sisters, believing themselves to be cousins, until Dolores moved away with her family. Years later, 16-year-old Irene discovers that she's adopted, and Dolores was her sister. To the best of anyone's knowledge, Dolores died in 1991, before Irene could find her; and Irene died in 2012, having located other family members.
- The whole case regarding Darlie Routier. Granted, everyone has their own opinion on whether or not Darlie is guilty, or actually innocent of murdering her own children. There is evidence suggesting she is the murderer, but at the same time plenty of evidence showing she is innocent. She currently sits on death row. If she is in fact innocent, and wrongfully persecuted, it means an innocent mother will be getting a lethal injection, while the real killer is out there walking free.
- The woman who suffered a brain aneurysm and lost 16 years of her memories! After leaving the hospital, she thought it was still 1960, but really it was 1976, her children had grown up, her husband looked different, certain family members or friends had passed away, her house was different, and to top it all off, she was fearful of admitting to her family she had lost her memory, until four years later. The segment ends with the host saying that doctors do not believe she will ever recover, or gain her memories back.
- The Missing Person case that involved the New Kids on the Block turned out to be this. It featured a missing girl who was supposedly caught on tape in the video for My Favorite Girl, so the Knight brothers (Jonathan and Jordan) showed up on the show asking for info about her whereabouts. According to an update, however, the girl on tape was an Identical Stranger... and the actual one had been murdered the same day she disappeared. The only good thing is that the poor girl's killer was found and brought to justice.
- The case of Joseph Schambier searching for his long-lost daughter Alberta Elaine; she was taken from him as an infant and put up for adoption when Joseph had been thought to have been mistakenly killed in World War II. Schambier learned Alberta died at the age of 18 in 1957, murdered by Alberta's estranged husband.
- The entire Tsunami Spirits episode from the Netflix revival, particularly the man who talked about losing his entire family and how he found his daughters.
- A moment from the episode "Stolen Kids" of the Netflix revival, where the mother of Shane Walker, breaks down in front of the camera, blaming herself for his abduction, because he was snatched in front of her.
- The cases of Kristin Smart and April Gregory. Both women were college students who disappeared on the same day on opposite sides of the country in 1996. Seeing April's father talk about how he cries everyday over losing his baby girl and how he knew she was dead was heartbreaking, and years later her remains and her killer were found and sentenced to 25 years to life. Meanwhile, both investigators and Kristin's family know who likely killed her, but can't arrest him due to lack of evidence. Making it all the more painful is how both he and his family continue to antagonize and harass her family over their grief even decades after her disappearance.
- While the Harper Ferry's steam trunk doe is considered one of the most frightening cases of the series, it's also this once you learn the details. As bad as it is to be gruesomely murdered and have your body hidden away without i.d, but to have a computer-rendered composite made just to figure out who you are since a visual i.d. can't be done is even worse. Moreso, one of the investigators surmised that the motive for the killing was that the man's only caretaker decided that they didn't want to help him anymore and felt that murdering him was the best option.
Tear Jerker / Unsolved Mysteries