Samuel asks Sam if Roy is just a "Red shirt" to him. The reference is to Star Trek (2009), where the crew in red shirts often die.
In Greek mythology Arachne was a human woman that was an expert weaver of silk and wool. She was the most talented weaver in all of ancient Greece and would boast that no one could weave with more skill than her, not even the goddess Athena. Athena was the goddess of craft and war, when she heard Arachne's boasting she became angered and appeared to Arachne, disguised as an old woman, and warned her not to boast about being able to beat a god. Arachne replied that it was not a boast, but a fact, so Athena dropped her disguise and challenged Arachne to a weaving contest to be judged by Zeus, whoever lost would agree to never weave again. Arachne's work turned out to be even more beautiful than Athena's, and Zeus proclaimed her the winner. This angered Athena, and to make matters worse, Arachne started to dance around and taunt Athena singing "I'm better than a god, I'm better than a god!" This caused Athena to become furious, so to teach Arachne, and anyone else that dared compared themselves to a god, a lesson she cast a spell upon Arachne turning her into a spider-like being. Her upper body remained human, but her hair fell out and her fingers and toes were turned into legs and her lower abdomen became like a spiders. Athena cursed her, and all her descendants, to live this way forever.
Upon entering Bristol, RI, Sam and Dean pass a sign for the city that says, "Where memories are made." Sam has lost his memories of the prior year after his soul was put back. In this episode, Sam's memories of his hunt in Bristol with Samuel slowly return.
Sam and Samuel use the names Agent Roark and Agent Wynand when first investigating the town. Howard Roark and Gail Wynand are characters from Ayn Rand's popular novel The Fountainhead.