Is "happily ever after" possible for Meredith Grey and Derek "McDreamy" Shepherd?
With Meredith experiencing a breakthrough in therapy - the realisation that she and Derek can be extraordinary together, rather than ordinary apart - she and Derek now face the highs and lows of being a committed couple.
Continuing their first year as residents at Seattle Grace Hospital, Meredith, Cristina Yang, Izzie Stevens and Alex Karev have interns of their own to mentor, including Meredith's half-sister, Lexie Grey.
Lexie has become a roommate and confidante to George O'Malley, who, after divorce with Callie, a breakup with Izzie and learning that he failed his residency test by only one point, is striving to get both his professional and personal life back on track.
After attending to his girlfriend Rebecca's mental illness on his own and revealing that he had gone through this with his own mother, Alex finds solace in Izzie's arms. Alex must continue through this difficult time, whether or not Izzie remains by his side.
Cristina, having finally won out over her tough-as-nails mentor, Erica, is back on track as a surgeon - but is there a chance for new love in her life as well?
With the encouragement of Mark "McSteamy" Sloan, Dr. Callie Torres has taken a chance on love with cardiothoracic surgeon Erica Hahn; now she and Erica must figure out what happens after the first kiss.
Overseeing the residents is the no-nonsense Chief Resident, Miranda Bailey. Facing marital troubles and the difficulty of balancing her work and personal life, Bailey has handed her responsibilities as head of the free clinic over to Izzie.
Also striving for balance is Chief of Surgery, Richard Webber, who has reunited with his estranged wife, Adele.
The doctors of Seattle Grace Hospital deal with life-or-death consequences on a daily basis - it's in one another that they find comfort, friendship and love.
Together they're discovering that neither medicine nor relationships can be defined in black and white. Real life only comes in shades of grey.