House and Cuddy are exploring the ramifications of those feelings and attempting to make a real relationship work. Meanwhile, due to a colleague's illness, Princeton Plainsboro is left without a neurosurgeon on site, threatening the hospital's accreditation as a Level 1 Trauma Center. As the team attempts treatment to get their sick colleague back to work, they discover there is more to the illness than they originally suspected and turn to House for direction. Instead, House remains elusive, leaving the team on its own.

A seemingly healthy 14-year-old girl collapses during a skateboarding exhibition; House and Cuddy face the challenge of handling their romantic relationship at work.

一个叫Margaret McPherson的病人因剧烈的疼痛和难以控制的呕吐而被送进医院紧急抢救。House和他的团队在替她治病的时候，竟意外地发现了她的「身份秘密」。在各种治疗方法均不见起色的情况下，House等人开始查找Margaret的家族病史以及她过去的经历。与此同时，House对Chase带来的新人十分冷淡，而House的「私人按摩师」的到来也令House和Cuddy不得不面对他们之间的新问题。

一个新生儿突发呼吸困难、肝功能衰竭等奇怪症状，House和他的医疗小组决定从孩子的母亲Abbey身上寻找原因。Abbey的一个决定可能同时影响到孩子和她自己的健康。与此同时，House迫于Cuddy的压力，不得不同意让Foreman和Taub雇用一名女医生顶替临时离开的「13」。Cuddy让House替她照看女儿，这让从没当过父亲的House和Wilson都犯了难。

选举季到了，选战如火如荼。新泽西某参议员的竞选经理在工作中突发急性肝功能衰竭症，伴随临时性的瘫痪。Cuddy命令House选择一位女医生临时顶替13的位置。当House不愿服从时，Cuddy自作主张，让三年级医科学生Martha Masters（Amber Tamblyn）加盟House的团队。House认为Martha既无经验，也无主见，可能会妨碍他的团队，但迫于Cuddy的压力暂时留下她。House为了治愈病人，不得不做出一个艰难的决定－－而这个决定可能危及他和Cuddy刚刚建立起来的感情。

少女在海中潜水发现了一个有200年历史的药罐。当药罐在她的掌心里碎裂之后，她开始产生类似天花的奇怪病症。House和他的团队刚刚接手这个病人，来自疾控中心的Dave Broda医生便下令封锁整座医院，并终止了House的治疗权。Masters（Amber Tamblyn扮演）怀疑Broda的动机不纯，并坚信病人所患的不是天花，而是另一种疾病。少女的父亲很快出现了相同症状，House被迫作出一个可能令自己丧命的大胆决定。与此同时，Wilson和Sam合作安抚一个正在接受化疗的六岁男孩。

Science and faith are called into question when a patient is admitted to the hospital following his reenactment of the Crucifixion. Meanwhile, Taub questions his wife about her relationship with an infidelity support group member, and the team attends a co-worker's wedding.

一个男人挺身救下一个掉进地铁轨道的陌生人，自己却毫发无损。正当人们为这神奇的一幕而鼓掌庆贺时，舍己救人的男人突然晕倒在地。House和他的团队担负起救治这位「英雄」的责任。全城的老百姓都很关注「英雄」的病情，然而House等人却从他的症状中发现了许多疑点。与此同时，House为了不与性格顽固的「准丈母娘」Arlene（Candice Bergen）见面而竭力躲避Cuddy的生日晚餐。Taub以「宣传大使」的身份为医院拍摄的广告照片引起了某人的注意，这大大出乎Taub的预料。正当Taub与妻子的关系有所缓和时，Masters（Amber Tamblyn）却以一个局外人的观点提醒他：该为他摇摇欲坠的婚姻做点什么了。

某少管所训练营中的教官和一名少年相继突发怪病，出现相似症状。House和他的团队接诊该病例后，无法确定真正的病因。Masters和House很快发现发病少年和教官有着特殊的「联系」。与此同时，Chase邂逅三个女人，其中一人将他的下流照片贴到社交网站上。Chase发誓要查出让他蒙羞的这个女人。Cuddy想让Rachel进入一家有名的幼儿园，但又担心她不够条件。为了讨好Cuddy，House私底下对Rachel进行秘密培训。

Cuddy’s mother, Arlene, is admitted to Princeton Plansboro after complaining about unusual symptoms, but stubborn Arlene insists that House be removed from the case, forcing House to come up with non-conventional means to treat his patient.

一名记忆力极好的女服务员总是出现暂时性麻痹症状。她的姐姐到医院去探望她，结果令她更为紧张，健康状况也急剧恶化。她的记性太好，总是对姐姐怀有强烈敌意。要想让病人配合治疗，House和他的团队必须首先修补这对姐妹的关系－－但Masters发现这件事远比给病人治病要困难。与此同时，Foreman帮助Taub准备考试。House决定帮助Wilson再找一个女人，但却发现Wilson身边已经有了一个「秘密同伴」。

House participates in a school’s Career Day and breaks a few rules by sharing explicit medical stories. Waiting outside the principal’s office, he meets two fifth-grade students who assess House’s relationship woes and try to help him understand how his selfish antics get in the way of showing Cuddy how he really feels.

一名普通的清洁工人，浑身上下长出可怕的疹子。House和他的团队在为病人诊治的过程中发现，此人对妻子不诚实：他一直骗妻子说自己还在做利润可观的房地产生意，而事实上他早就破产了。与此同时，Cuddy获得一项殊荣并被邀请参加慈善晚会。Cuddy想让House陪她一起去，House会在宴会上如何搅局？Chase和Masters给彼此上了一堂关于「公与私如何有机结合在一起」的「课程」。

Tension reaches new heights when Cuddy faces sobering news that propels her to reevaluate her priorities. While House is distracted by his concern for Cuddy’s well-being, the team treats a teenage patient whose worsening symptoms and suspicious body scars indicate more than just physical illness.

一位年轻的职业斗牛冠军在斗牛场上不慎受伤，被人送到医院急救。House的团队经过多次检验，均不能确诊他的病因，只好向正在处理「私人事务」的House求助。斗牛士的情况持续恶化，一些旧的症状突然消失而新的症状不断出现。House的团队决定孤注一掷，对其实施心内直视手术。与此同时，Masters对斗牛士产生了爱慕之情，这让Taub颇为惊讶。

有人发现一个无家可归的年轻人躺在公园里，身上有可怕的疤痕，胸口有烧伤的痕迹，而且嗅觉已经失灵。House和他的团队接诊这名病人后，发现他曾经是个瘾君子。他们决定从病人的个人记录和家庭历史中寻找造成他今天这副模样的真实原因。与此同时，Cuddy向Wilson倾诉心中的郁闷，称她为主动结束她和House之间的关系而感觉不安。

监狱门口House迎接着「13」出狱，然而House真正感兴趣的是「13」入狱的原因。但「13」始终守口如瓶。House带「13」参加一年一度的土豆枪大赛，他们与一个远比House年轻、自负的强势对手展开激烈竞争。与此同时，House的医疗团队正在紧急抢救一名患急性呼吸疾病的理科教师。当他们实在没有头绪时，只好去患者家中寻找线索。他们发现患者有收藏癖好。另一方面，Taub开始寻找新的爱情。

Masters faces a career crossroads on her last day as a medical student and struggles with the choice to continue on the path to become a surgeon or to accept the rare opportunity to join House’s team officially. Meanwhile, the team treats a 16-year-old girl who inexplicably collapsed days before embarking on an ambitious sailing tour around the globe. Despite the patient's life-changing diagnosis, the patient's family insists on getting her back on the seas in time for her potentially record-breaking launch. But to the team's surprise, including House, Masters makes a bold decision regarding the patient’s treatment.

获得巨额彩票大奖的Cyrus Harry试图寻回失散已久的爱人，但却因局部麻痹症被人送进医院急救。当House等人对Cyrus进行诊断时，Cuddy的母亲宣称自己要控告医院违反规定及失职，令House和Cuddy面临失去医生执照的危险。Chase和Foreman打赌，称他有多种方法来难倒对方。

After losing a bet with Wilson over a boxing match, House is convinced that his fighter has an underlying medical condition that cost him the fight. While he tries to prove it, he leaves his team alone to help a bomb scientist who suffered a seizure. Meanwhile, House may be experimenting with a new drug to help his leg pain.

When House discovers that the experimental drug he's been using causes fatal tumors, he decides to attempt to excise them himself. However, he can't complete the surgery and ends up needing Cuddy's help. Meanwhile, Thirteen's friend from prison (Amy Landecker), a relapsed drug user, arrives at her apartment needing medical care after being stabbed. With her friend unwilling to go to the hospital, Thirteen enlists Chase's assistance when the friend loses sensation and movement in her arm. Also, Taub receives some unexpected news that could change his life.

行为艺术家在表演时突然晕倒，她所有的症状好像是经过精心设计。House和Cuddy的关系也非常微妙，冲突之下House竟然毁了Cuddy的家庭宴会还有她的房子。