The doctors of Seattle Grace are called upon to man up when a stampede at a comic book convention causes an influx of colorful characters in the ER - blurring the lines of fantasy and reality; Mark shows his softer side with baby Sofia when Arizona and Callie go out of town, but at work he continues to give Jackson a hard time; Ben returns to the ER, only to find that Nurse Eli has moved in on Bailey; and the male doctors bond over their frustrations with women.

After being blackballed by most of the surgeons, Meredith uses Lexie to spark Derek's interest in her patient's rare brain tumor case and, in secret, gives guidance to April with Bailey's clinical trial; Callie's wish for Arizona and Mark to form a friendship comes to fruition and she realizes it's more irritating than helpful; Alex and Teddy research alternative surgeries for a very superficial patient; and Callie and Cristina struggle with a very difficult spinal surgery.