Everyone in the ER is trying to cope with the loss of their colleague. The staff feels defensive toward the new Chief and her tough disposition. Gates and the new interns treat a bio terrorist who has a lethal secret that endangers them all. Neela makes a great effort to get Dubenko back on the surgery staff, and gets help from an unexpected source.

Dr. Banfield defends herself during a mugging. Dubenko returns to work, due in no small part to Brenner's organized protests. A young gymnast comes into the ER with injuries consistent with a fall, but Banfield and Gates each think a different family member may actually be to blame. Sarah neglects to ask Gates's permission before getting her tongue pierced.

It's Halloween night, and the interns continue to be paired with the residents. Gates's teaching methods with Daria, and her responses, belittle Sam. A school fight results in a stabbing and a nose that won't stop bleeding, with Brenner treating the victims and being deeply affected by the truth behind their confrontation. The staff, especially Neela, are enthusiastic about a surprise visitor. Gates gets locked in a maintenance area with a quiet young boy.

Chaz, now a med student, begins his ER rotation. Morris takes him under his wing and shows him some risky procedures, endangering a patient and raising Banfield's ire. Neela becomes upset when Banfield questions her authority and skills in front of her intern. Gates invites Sam and Alex to move in with him and Sarah.

Sam gets frustrated with Gates when he gets obsessed with finding a homeless war hero. Neela is upset at her intern after he gets the entire surgery department into a lawsuit. A husband and wife come into the ER after someone tried to burn down their home. Brenner loses his cool with a patient and it gets physical.

A package for Morris from his deceased father is delivered to the ER. Sam has some anxiety over Alex being removed from the ventilator. A woman with a high-risk pregnancy worries that she will be deported. An old friend returns to celebrate the holidays.

When a drug deal goes bad, two brothers sustain serious injuries and are brought to the ER. Tensions continue between Gates and Sam, coming to a head when Tony is the last to know Alex is about to be released from the hospital. Neela has to tell a young girl with sickle cell anemia that she must have an operation, and the case leads her to consider specializing in pediatric surgery. A feisty patient takes Morris into her confidence. Banfield ponders her choices about expanding her family.

Morris faces a complicated case involving a young girl hit while riding her bicycle. Gates finds it very difficult to let go of his feelings for Sam. Neela becomes quite flustered when Brenner returns from Australia.

Neela and Sam are shocked when they arrive back to the airport with transplant organs only to find that their plane has left them. Dr. Carter gets a surprise visit from an old friend while waiting for his kidney transplant. Dr. Banfield bonds with an abandoned baby boy that is left at the ER.