- Luli's death in "Anslo Garrick", and the way Red desperately begs for her life (as well as Dembe's, who is spared only by chance) from both their killer and Harold (who can give Garrick what he wants by telling him the access code to the box Red has locked himself and Ressler in).
Red: Have you sailed across an ocean, Donald? On a sail boat surrounded by sea with no land in sight. Without the possibility of sighting land for days to come. To stand at the helm of your destiny. I want that one more time. I wanna be at the Piazza de Campo in Siena and feel the surge as 10 racehorses go thundering by. I want another meal in Paris at L'Ambroise on the Place de la Loge. I want another bottle of wine... and then another. I want the warmth of a woman in a cool set of sheets. One more night of jazz at the Vanguard. I want to stand on summit and smoke cubans and feel the sun on my face for as long as I can. Walk on the wall again, climb the tower, ride the river, stare at the frescoes. I wanna sit in the garden and read one more good book. Most of all, I wanna sleep. I wanna sleep like I slept when I was a boy. Give me that... Just one more time.
- Red talking to Ressler when they were locked up in the former's cell, talking about how he just wanted to have a normal life with a family instead of being an underworld figure.
- Liz asking Red if he's her real father after Anslo Garrick was killed, despite the latter telling her that she can't believe everything he says because he's a known criminal.
- The deterioration of Liz and Tom's relationship over the course of the series. With the revelation that he is really an assassin/spy, which confirms Red's accusations to Liz.
- Ressler's heartbroken expression after Audrey gets shot and dies in his arms.
- Poor Liz finds Meera just seconds before she dies...
- Cooper's growing frustration that the military would conduct experiments against innocent, average Americans in "Dr. Linus Creel".
Cooper: I love this country. But every once in a while, you hear about something like this. Some bone-evil crap that's almost inconceivable. That's what I hate most about this detail. Reddington pulling up the carpet and shoving your nose deep into the filth. After a while, it's all you can see.
- Reddington smiles as he watches an old film about his family at the end of 'The Front', renewing his quest to find his estranged child.
- At the same time, Liz looks at Carrie Anne's baby while thinking about the life that she lost.
- When Reddington sees his wife for the first time in forever when Berlin releases her to Reddington after he blackmails Berlin. The look on Reddington's face when she walks forward...that's repressed longing.
- Ressler's breakdown at the end of "The Mumbasa Cartel" when Liz reveals she found the pain pills he's become addicted to. After an entire season and a half's worth of relentless trauma, it's the first time he's ever showed vulnerability to another character, and it's heartbreaking. The fact that the whole thing is done without speaking, from a distance, just serves to emphasize how alone he seems, and then Liz putting her hand on his shoulder brings on the waterworks.
- Alan Fitch's death. Alan Alda's performance in that scene really was a One-Scene Wonder. In his last moment, the man remembered all 763 people died "in service of their country" in his order and decided to not make it 764 by telling the bombman that's trying to remove his collar bomb to go. He then requested a meeting with Reddington, telling him everything about his faction's plan for 2017 and told him that they have 51 wonderful years together.
- Berlin's last meal (or in this case last Vodka). He calmly drank with Reddington, cup for cup and spoke about his pride to be a Soviet citizen when he watched a parade as a boy and then silence. Even more tearjerking when you considered that this is Truth in Television, many many Soviet and other former's communist countries's citizen felt the same pride and the same emptyness and hopelessness when The Great Politics Mess-Up happened.
- Berlin's last meeting with his daughter.
- Liz painfully calls out Reddington for recklessly risking his life near the end of "T. Earl King VI (No 94)".
Liz: Has anyone ever helped you? Is that why you are the way you are? Because you don't feel deserving of it? Is that why you can't be vulnerable for a second? I risked my life for you because I care about you.