I don't really watch it religiously, but there are a few cases that really break my heart.
Angela Hammond. This happened in 1991, and there have been no updates since. She is very clearly dead. Most likely raped and murdered within hours of being abducted. If you watch the segment on Youtube, you'll see an interview with her boyfriend. He was trying not to cry during it.
Cindy James. This one is just fucking scary. I sort of thought she was unstable and doing it to herself until the end. There is no way she was able to inject herself with morphine and then tie herself up that way. I can't think of much worse than being stalked and harassed and having no one believe you.
Mabel Woods dog kennel fire. Being an animal lover, this one actually made me cry when I saw it on TV. I turned it off right afterwards and had to do something less depressing.
These are just three that upset me, there are plenty more!
And obviously, Robert Stack > Dennis Farina.