第三季结尾，蒂娜盛怒决定独自抚养小安。第四季的开篇，贝蒂带着小安惊恐地逃跑了。随后贝蒂当上了加利福尼亚大学艺术学院的新一任校长，拥有一大批年轻的爱慕者。她邂逅了在艺术方面才华横溢的茱蒂（马莉·马特林 Marlee Matlin饰），开始有意识的接近茱蒂，被她深深的迷住了。逃婚的夏恩开始了纸醉金迷的浪荡生活。凯特因为感情问题，开始酗酒。塔莎要回伊拉克执行新命令，这让爱丽丝很难受。詹妮自从马克斯做了变性手术之后裂痕产生。她开始着手《Lez Girls》的写作，连载成功，小有名气。可《Lez Girls》描写的都是这群朋友们的个人生活，詹妮在故事里涉及了很多大家的隐私。这让大家备受困扰，麻烦不断。In the aftermath of the events in Canada, Bette is on the run her infant daughter, Angelica, while a vengeful Tina tries to track them down. However, a serious intervention from Joyce Wischnia makes them re-think their situation for baby Angelica's sake. Shane returns to Los Angeles after her abortive wedding to Carmen and reverts back to her old bad habits of drinking and drugs while staying at the debauched Cherri Jaffe's beach house. Later, Shane gets a surprise visit from her father's wife/stepmother Carla. Meanwhile, Helena tries to get used to living without her mother's money with Alice's help. Max attends a support group for his newly expressed gender identity, while Kit has trouble with her pregnancy and must struggle with a hard decision for an abortion with Angus's support. Also, Jenny's semi-autobiographical book finally gets published and she has a book signing at the Planet with Claude in attendance, and gets a surprise when her former flame, Marina Ferrer, also shows up.
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