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Die Serie erzählt die Geschichte von fünf jungen Assistenzärzten des fiktiven Krankenhauses Seattle Grace Hospital in Seattle. Im Mittelpunkt steht die junge Ärztin Meredith Grey, die zusammen mit ihren Kollegen Cristina Yang, Isobel „Izzie“ Stevens, George O’Malley und Alex Karev ihre Ausbildung in der Chirurgie absolviert. Im Kern der Handlung stehen die verschiedenen Beziehungen der Assistenzärzte untereinander und mit ihren Stationsoberärzten.
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