Picking up where "A Change is Gonna Come" left off, a sexy Meredith and Derek are enjoying life as friends with benefits... or as they call it, S&M (sex and mockery). But Derek, like everyone else on the show on this night, is fighting an addiction that's very difficult to break.

It's all about addictions, for better or for worse, and as the episode begins, George is elated after telling Izzie he loves her too. He admits marrying Callie happened too fast, and resolves to end it. Izzie is very happy to hear this, but changes her tune later when Callie is mean to her in the operating room.

She's got to work under Callie, after all, and having a bomb like this dropped on her wouldn't exactly be good for Izzie's career. She tells George to wait, and they almost - almost - kiss again at Seattle Grace. O'Malley is determined though, or so he says, not to be that guy. But Callie ends up having the day from hell and asks George to please, please not give her any bad news tonight. He wimps out, and the secret remains secret for at least another day.

When we first see, Cristina is auctioning off her wedding gifts from the ceremony that wasn't in exchange for surgeries. She ends up giving a good one away to a resident in exchange for a cover story, though, when Mrs. Burke walks in and Cristina hides. Cristina sends Meredith to get rid of Preston's mom. But Meredith is as ineffectual as her tiny fists.

Mrs. Burke lets Meredith have it for her “It's over, it's over, it is so over” moment at the wedding, saying that makes her either insensitive or downright vindictive. George then sees Mama Burke and talks to her a bit about Preston. But really he's talking about himself. She can tell, being wise, that George is staying in his marriage out of obligation, and says that is no way to live or to love.

Derek, too, runs into Mrs. Burke and has an interesting talk with her, one we will get to in a moment. But when Cristina finally approaches her, she is surprised at some of the things she hears. Mrs. Burke is here to collect her son's things, but she's also sorry - that Cristina lost Dr. Burke as a mentor. She commends her for being a strong woman and says that if it were a different era, she may have been more like Cristina herself.

If there's one thing Richard Webber is addicted to, it's work. But he is determined to delegate more so that he can spend more time with Adele. All that goes out the window, though, when five patients are brought into the hospital after a gas main blew in an apartment building. But how?

Alex examines an 18-month-old baby, and orders a toxicology test done on him after sniffing the baby's head. When the nurse comes back with the results, he learns the baby is on meth, ingested gradually over the course of time. His parents are running a meth lab out of their apartment.

George calls a code blue when a patient who was at the meth lab, Clark, crashes. This episode is very much about literal addictions as well. An addiction to meth is serious, and Clark begins to go through withdrawal. Surgery might still be an option for him, though, but eventually his internal bleeding is too much for his body to take and he dies.

Miranda wants a resident to oversee the clinic, but Callie won't hear of it. Bailey resigns herself to sending Lexie and another new intern to the clinic, but begs - cajoles, guilts, pushes - Meredith to go babysit them after she sees their incompetence. Lexie is excited to see Meredith, but the latter is significantly less pumped about it.

In the clinic, Lexie tries to make conversation, but is quickly put in her place when she remarks that she and Mer have the same dad. Meredith says they did not share the same dad because Thatcher left her she was five. Does that sound like her dad too? Mer admits she's got serious problems when it comes to attachment and would rather not know the person her dad chose over her, to be perfectly honest.

Things get really interesting when Alex is treating the baby and Dave, his father, who runs the meth lab and is in the hospital for minor injuries, frantically yells at it to stop crying. Alex's rage against what Dave did to his son (as well as at his own dad, perhaps), surfaces as he screams at Dave that he's a terrible father for raising his son in a meth lab. Dave knocks Alex out with a blow to the head, grabs the baby and bolts.

As Chief Resident, Callie is responsible for Alex's behavior. Callie looks everywhere for the missing baby. She runs into Mark, who tells her in as many words that she needs to confront George, who she admits she thinks is cheating on her, rather than letting it ruin her career. Eventually, Derek is the one who finds the baby, who is alright despite suffering a stroke. At age one. Don't do meth, people.

Derek is reeling after Mrs. Burke told him that he needs to stop feeling sorry for himself, and not to take any less than he deserves. He confides to Mark that he has a problem... it's not a drug problem, but he's very much addicted to Meredith. He has Mark tell her that he can't meet her for the usual night of sex and fun without commitment, but changes his mind at the last second and runs after her. Sometimes letting go just hurts too much.