Like Vol. 3, Vol. 4 is split into two stories. First is the three issues the volume takes its name from, "Safeword." Safeword played much differently for me the first two times I read it, and I wasn't really sure if it had succeeded in its goal. But we're always different people when we read things over and over, and I think I finally get what this issue was going for, even if it's not my favorite.
Yorick and Co. have a sick Ampersand on their hands, and so 355 leaves Yorick in the capable hands of her former colleague, 711, while she and Dr. Mann take Ampersand to the hospital. 711 has been in retirement ever since her husband died in the plague. 711 takes it upon herself to cure Yorick of the secret suicidal tendencies he's been harboring since the day all the men died, and it gets super weird and disturbing (I'm thinking particularly of an image involving a tissue and some flies). 711 subjects Yorick to a form of aversion therapy that at first looks a lot like torture -- and which makes us assume that she's actually one of the bad guys. What she's actually doing is forcing Yorick to confront his own hang-ups, and by the end he realizes that he actually doesn't want to die (although the vision that he sees that convinces him to live is withheld from us, for now at least).
The second story in Vol. 4 is "Widow's Pass." Yorick, 355, and Dr. Mann have made it all the way to Arizona, which is now apparently controlled by some fringe psycho militia called the Sons of Arizona, who think Arizona is more important than "the rest of the union." They also believe that the federal government is responsible for the plague and in retaliation have taken control of the highways. A bald (by choice) mechanic lady named PJ takes them in, and when Allison stupidly tries to make a deal with the crazy militia ladies, a whole bunch of shit hits the fan, and yet another woman is killed because she had the misfortune to meet Yorick Brown.
All in all, this isn't the best book in the series, but both stories start the process of plumbing the emotional depths of what has happened, and that's a process that will continue throughout the rest of the series.