生活不会一片坦途，更多时候是像在变化万千的大海上航行，时而风平浪静，时而波涛汹涌。而人生40也恰如生命之舟驶进了多风多浪的海域。知秀是大韩民国众多的普普通通的家庭主妇之一，在生活中她要扮演人媳、人妻、人母的角色，终日围绕着家庭忙忙碌碌，过着乏味而波澜不惊的日子。但知秀觉得踏实和满足。花英是知秀高中同学，也是知秀最要好的朋友，她的生活完全另一番景象：年少时移民美国、本人是整形外科医生、生活中涂满了华丽的色彩；但如今丈夫自杀，事业破产，陡然跌入人生低谷的她只身回到韩国……
张路(徐路饰)全力抢救一个叫小敏的受伤女患者，张路尽了最大努力，但小敏还是因为大出血而离开了这个世界。小敏的母亲杜丽(宋春丽饰)悲痛欲绝，对张路兴师问罪，认为是张路的失职导致女儿的离去。杜丽的身后站着一个更具威胁的人物，小敏的继父全武(姜武饰)，身为伟业药业集团董事长的他，在这个城市是手眼通天的人物。但他意外发现张路竟然是5年前被自己撞伤的同事张文学的女儿。杜丽以报复杀人罪欲将张路送上法庭，却被老谋深算的全武制止，他这样做是为了掩盖一个5年前的秘密。
As Leo's replacement Thomas Chamberlain arrives Nikki investigates the murders of Rachel Freedman, shot in the head, and her little autistic son Nathan, who was poisoned. Nikki rejects policewoman Anne Burchett's theory that Rachel killed them both but is perturbed when an impostor, claiming to be Rachel's sister, visits the morgue. At the same time the disfigured corpse of Eva Liron is discovered, killed with the same poison as Nathan. She had been the nanny to French hot shot footballer Isaac Dreyfus and was planning to blackmail him over a sex tape of them both. Jewish Isaac is a controversial figure due to his anti-Muslim sentiments but he denies ant part in the murders. Then another victim, Isaac's agent Mousa, is discovered dead.
