The prize: ending the Apocalypse. The price: Sam's life. Season 5's horrific finale left Dean alone, as Sam descended into Hell. Now a different man, Dean vows to stop hunting and devote himself to building a family with Lisa and her son Ben. Then, mysteriously, Sam reappears, drawing Dean back into the old life. But Sam's a different man too. He's returned without his soul. How the Winchesters confront this greatest challenge yet to their powerful bond is the troubled heart - and soul - of the profound and thrilling 22-Episode Season 6. As the brothers struggle to reunite, they must also battle deadly supernatural forces. Demons. Angels. Vampires. Shapeshifters. And a terrifying new foe called the Mother of All.

迪恩（简森·阿克斯 Jensen Ackles 饰）和萨姆（贾德·帕达里克 Jared Padalecki 饰）终于找到父亲约翰（杰弗瑞·迪恩·摩根 Jeffrey Dean Morgan 饰），但为了救迪恩，约翰甘愿深入地狱，留下兄弟两个继续完成“猎人”职责。同时兄弟俩也了解到“黄眼恶魔”的存在，开始一路追踪这个最大仇人。二人解决了一个又一个超自然生物，兄弟二人的性格、理想分歧也一直存在，不时吵吵闹闹。但萨姆终究是黄眼恶魔的唯一目标，为了萨姆可以好好活下去，迪恩不惜和恶魔做交易，用自己的灵魂换回萨姆的生命……