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Okay team. Let's spend a few sentences getting you all caught up, because time travel. Okay, here's what you need to remember: Dr. Katarina Jones, in a post-apocalyptic 2043, discovered that there was a vast conspiracy to release the global epidemic that wiped out humanity and so she created a machine that can send people back in time to try and stop it. The man who seems destined to do that, based on lots of different factors (including an encounter between Cole and Jones back in Episode #12) is Cole, who was sent back in time and fell in love with Dr. Cassie Railly, the person who historical records indicate was a key figure in identifying the virus' origins.
Now, there's also Ramse, who was Cole's friend. Ramse realized if the plague was stopped, it would erase the future and thus erase the existence of his son. So, Ramse went back further in time and became one of the architects of the plague. He was a good guy, then a quadi bad guy (with good motivations), and then Cole saved his life and now, he's a good guy again and he and Cole are working to stop the coming global plague that's about to be released by Jennifer Goines. She is pawn of the Army of the 12 Monkeys (the organization that wants to start the plague), but they seem to be brainwashing her into believing this is her destiny (we should mention Jennifer's a little unstable. She hears voices. She's quite easily manipulated).
So, in 2016, Cole and Ramse are running from the Army of the 12 Monkeys, who are all taking orders from someone called "The Witness." The problem is that once Ramse and Cole thwart Olivia, a member of the Army, on a bridge in Budapest, things that haven't been foreseen by "The Witness" have started to happen. Ramse and Cole have been on the run for three months now, disagreeing about what to do next. One thing they DO know is that Ramse has a tracking device implanted in his neck and that needs to come out or the Army of the 12 Monkeys will find them.
Back in 2043, Cassie wakes up to find that she was shot in 2016, but Cole sent her forward in time (remember? In the Season 1 finale?). And now he's stuck in 2016 because he has none of Jones' injections, which would allow him to splinter forward in time. And things are grim. There's a group called "The Messengers" who want to use Jones' machine, but nobody's sure why. When they try to get Jones to help them, she sets the first person on fire by splintering only part of him.
The Messengers figure out how to use the machine without Jones' help and start sending more and more people through time while back in 2016, Cole finds Dr. Kalman, an old friend of Ramse's from Markridge (the people who made the virus) and asks him to come help Ramse. When Dr. Kalman operates on Ramse in the sewer, he also injects Ramse with a serum that paralyzes him. And now, Dr. Kalman is going to deliver Ramse to the Army of the 12 Monkeys in exchange for protection from the virus. Cole's not having any of this. He kills the doctor and off he and Ramse go.
In 2043, Cassie meets Deacon. He used to be a kind-of bad guy but now is in a temporary partnership and is responsible for Jones' protection detail. Cassie diagnoses Deacon with Wilson's disease, which is too much copper in the brain and liver. She offers him medicine from the past if he will help her escape the Messenger's holding cell. He locks her up anyway, and then comes back shortly thereafter and springs her, forcing her to kill one of those Messenger people.
Ramse reveals to Cole what Dr. Kalman told him – that Jennifer Goines is planning to release the virus on Chinese New Year in New York City. So they go and try to find her, but she's gone completely off her rocker and is at a speed-dating event, where she asks a dude that's on Impractical Jokers to kill her before she releases the virus. He calls 911 and she flees.
In 2043, Deacon and squad blow up the machine. Like, kaboom. It stops any more Messengers from going through and kills the rest of them who haven't already gone back in time. Cassie is now stuck in the future and Jones is going to rebuild the machine.
In New York in 2016 on Chinese New Year, Cole and Ramse find Jennifer Goines, who seems thrilled that someone has come to stop her. Faith in humanity restored! But there's a hitch – even though she wants Cole to kill her, he can't seem to do it. And poor crazy Jennifer is torn between releasing the virus - which she has been convinced is her "destiny" - and listening to Cole, who actually seems to care about her. And then, when the Army of the 12 Monkeys turns up, Cole is screwed until a gun-toting Cassie arrives from the future. The future has changed her. Cassie kills ALL the bad guys, and now she and Cole have a choice to make, kill Jennifer like Cassie wants to, or protect her like Cole wants to. They face each other, guns drawn.