Who was able to pull the strings to get the X-Files reopened? Was it Skinner? Does Skinner even have that kind of power at this point? After all, he’s been an A.D. at the FBI for two decades without moving up, and this was clearly something people in power—AKA Cigarette Smoking Man—didn’t want to happen. Was getting Mulder and Scully back into the mix a vital starting point for this outbreak?
Speaking of Skinner, was he immune to the plague? Maybe he was immune, thanks to his previous infection with nanotechnology. Or...is he out there dying?
Who saved CSM after he was burned alive in the 2002 series finale? And why did they choose to save him if this was already in play? (Also, how the heck did he survive that missile blast? He should absolutely be dead.)
Why did CSM get Reyes to be his helper? They had no connection, outside of her time on the X-Files, and in theory, she could have bow his cover by immediately going to Skinner, Doggett, or Mulder and Scully.
When did Reyes and Doggett split up? The 2002 series ended with the agents fairly close, so at what point in the years after the finale did their paths diverge enough so that she would take CSM's deal and leave behind the entire life she had before?
Why didn't CSM give Mulder the cure without his consent? Obviously, CSM wants Mulder to agree so they could be partners at “the big table." But, if CSM truly wants Mulder alive, he could have made it happen...even if it would torture Mulder to survive the outbreak, knowing how many people died. Near the end of their time together, Mulder was so weak he wouldn't have been able to object to the cure.
Also, how could Mulder, an alien abductee himself, not have alien DNA? Was his abduction different than Scully’s? Was she abducted/tested by men, whereas Mulder was actually taken by aliens? Or was Mulder specifically chosen to not get the alien DNA?
Does William hold the key to curing Mulder? What impact did the magnetite—which William was given as a baby to “cure” him of being half-alien—have on Scully and Mulder's son? Does William actually have the tools in his stem cells that Scully thinks he does?