Meredith and George are experiencing morning-after tension at home and at work and it has the rest of the doctors wondering what's up. Derek and Addison are experiencing their own version of morning-after tension as a result of Mark's visit to Seattle. Bailey, returning the favor that was done for her during the Code Black situation, must treat Addison for a specific feminine problem. Izzie and Alex are making headway in their relationship until Denny Duquette comes back. Soon Alex is not-so-oddly jealous of the attention Izzie is showing to Denny. Someone finds comfort in confiding in a patient who is going through an ordeal of his own. Burke deals with a patient and gets to observe the patient's unstable relationship with his fiancée.

A patient is in the hospital because they fell asleep in a hazardous situation. A patient's home laboratory blew up in an apartment building and the victims flood the hospital. Alex investigates the cause of the incident by talking to a really old guy who lived in the building. Jane Burke shows up to deal with what her son left behind. Lexie tries to talk to Meredith. Callie is overwhelmed by her new position while Bailey is searching for things to do.

The doctors meet the world's oldest intern. Marcy brings in her son Henry because she finds his change in behavior suspicious. A patient named Connie may lose her vocal chords unless Mark and Richard can perform a radical new surgery. George impresses the other interns at work but at home he is trying to deal with his guilt about having sex with Izzie.

It's Halloween at Seattle Grace! There may be jokes, pranks, and/or scare tactics. Some of the women form a club based on an experience they all share. A man volunteers for what most of the doctors believe is an unnecessary surgery. One of the patients is in the hospital because they tried to carve a pumpkin in an unconventional manner.

There has been a bus crash and the patients are in the ER. Meredith and Derek's relationship gets more complicated when he dates a fellow doctor. Meredith's dad goes to visit her at the hospital.

An ambulance crash endangers the lives of the paramedics involved, as Meredith and the Chief work on-site to save them, Bailey treats a patient who refuses her help, and Ava returns for Alex and meets his other girlfriend in the process.

Meredith works furiously to save a paramedic trapped in an ambulance; Lexie holds the life of a patient in her hands; Derek must rely on a nurse to save a patient; Bailey struggles to balance her personal life with her work.