Nicole, desperate to get back to the Glamazons, tries to bribe and blackmail Principal Krupps. Her attempts fail and she gets Mary Cherry and Sugar Daddy to help her make a fake video about him. As a result, she gets terminated from the cheerleaders forever. A new kid joins Kennedy High and gets a spot on the football team. Josh, jealous of him, tries to put everybody else against him. He gets his mom a job at school and she starts to date the football coach, and Josh's life falls apart. Sam misjudges George but realizes that friendship is more worth than an article. Josh finds Nicole crying, a proof that she still has a human side. They console each other.

Nicole is desperate to save her popularity, which is falling since she was banned from the Glamazons. She tells Brooke that she should dump Josh and start dating George. Harrison is feeling a little bit jealous about Sam and George flirting, and so he and Nicole team up to make a study on attraction for chemistry class. Brooke and Josh break up. Sam feels like she lost again to Brooke when she sees she and George together. But George tells Sam he is really into her and they kiss. Josh and Lily find themselves attracted to each other when he helps her to send a gay chimp back to his lover in Uganda. Harrison learns more about Mary Cherry and starts to have feelings for her (could it be love?). Jane tells Mike she's pregnant.

Sam decides to take her relationship with George to the next level, and he gets scared and says they should wait until they're both ready. Bobbi Glass decides to make all her students act in a play she wrote herself (""That Burning Sensation: A Cautionary Tale"") about STDs, as a part of the ""National STDs Week"". The students are cast: Lily as gonorrhea; April as syphilis; Josh and SD are worrisome warts; Mary Cherry and Nicole are crabs; Brooke is herpes; Carm is unsightly yellow discharge and Sam gets the part as the whore, with Harrison (now back at school) as the lonely virgin. Josh and Sugar decide to give Harrison a ""virgin certificate"", since he is the only virgin boy in the group, but he gets offended and embarrassed. Instead of taking the certificate, he decides to ask Nicole to sleep with him, but she says no. so he decides to use his certificate, but the prostitute is so old that they decide just to have Chinese food instead. Lily runs into George at a clinic and finds out he

Nicole's mom is not so happy about her spending time with her birth mom. Judy Julian tries to bribe Nicole's mom so she would disappear. Shaggy leaves and Nicole and Judy become closer. Meanwhile, the girls are bored with the immature behavior of the boys and their boring lives as high school students. Brooke meets a college girl who invites them to a college party. Sam and Lily are stuck at home for lying about where they where going and spend up playing board games with Sam's parents all night. Carmem meets a boy and goes up to his room. Feeling that something might happen, she hides inside the closet until the boys come to rescue her. After their experience at the frat party, the group learns that high school isn't so bad after all.

Lily, in an effort to defend a fellow student who has been suffering jokes about his lifestyle, starts the G.L.A.S.S. (Gay and Lesbian Alliance of Supportive Students), which causes a lot of repercussion around the school, and not such great support from people as she expected. But prejudice is not only about sexual choices, as Sam and George have to deal with the comments on their interracial relationship; Sugar D. doesn't get a job for being fat and Jamie (Brooke's date) reveals that he has suffered prejudice because of his religion. Things get hot when Lily is hospitalized after being attacked when she was leaving a g/l community center (which she took Miss Glass to get information about her sexuality). The gang realizes that hate will never lead to anything, and join the group one by one. Bryan comes out of the closet in a gesture of support after the group is cancelled.

Ms. Glass wants all the students to write down where did they go for Spring Break and how many they slept with, so, in her own words, she can judge them. Most of the gang say they went to Cancun, and Harrison writes that he went to Yemen as his nose starts to bleed. Ms. Glass deduces he has been infected with the Rift Valley fever that is contaminating everyone in Yemen. Just as Sam was trying to talk to him by his locker, they are both isolated from the rest of the people and the school is shut down in quarantine. During Chemistry, Mary Cherry receives a call in her cell phone from someone who knows what she really did for Spring Break - a low-budget soft porn scary movie - and she has to run for her life as she is chased to be killed. Meanwhile, Lily tells April what they really did for SB. They intended to go to Cancun, but they all stayed in LA and had SB in different ways. Nicole is elected to attract the killer, but since she's not a virgin, and only virgins get chased by killers

Sam and Brooke have a quick but intense argument over what each one has done to/with Harrison. Sam does not forgive Brooke for having slept with him, and Brooke puts Sam against the wall saying Sam turned him down so there were no strings attached. They both realize none of them is really wrong, and if there's anyone wrong there it's Harrison. At school, they give him the cold shoulder and George does the same to Sam. Sam and Brooke plan to stood up Harrison at a restaurant, but Brooke shows up and is caught by Sam talking to Harrison, which leads into a huge food fight. At home, Jane is trying to fix things between the two of them when her water breaks. Josh's mom announces she is moving away, and Josh has to either come with her or go live with his dad - which he does in order not to leave Lily. She suggests they get married, and although his mom tried to warn him that he was too young, he goes ahead and gets married to Lily right before prom. Mary Cherry accidentally bumps into Big