Two brainy best friends, Leonard and Sheldon, could tell you anything you want to know about quantum physics—but when it comes to dealing with everyday life here on Earth, they're lost in the cosmos. In the series premiere, when Leonard and Sheldon meet a free-spirited beauty named Penny, Leonard is immediately interested in her. But Sheldon feels his friend is chasing a dream he'll never catch.

After Leonard tries to do a favor for Penny, Sheldon ruins the plan. Leonard volunteers to sign for a package, hoping to make a good impression on Penny. However, when he involves his obsessive-compulsive roommate, Leonard sees his attempt at chivalry go horribly awry.

Leonard is depressed to learn that Penny is dating someone. As a result, encouraged by his friends and fellow scientists, Leonard actually summons the nerve to ask a woman out on a date. Recurring guest star SARA GILBERT ("Roseanne") appears as Leslie.

After being fired from his job, Sheldon attempts to explore the "dreadful" life beyond physics. But his initial thrill of shopping with Penny devolves over time to him weaving ponchos as a shut-in, forcing Leonard to call on Sheldon's mother, Mary (LAURIE METCALF - "Roseanne").

After sensing that his pursuit of Penny isn't going anywhere, Leonard agrees to an unexpected sexual encounter with fellow scientist Leslie Winkle (recurring guest star SARA GILBERT). The one-night stand throws Leonard and Sheldon deep into uncharted social waters.

The socially stunted guys are nervous when Penny invites them to a party she's hosting. But they are ecstatic to find out that it's a Halloween party and enthusiastically don their respective nerdy costumes, which unfortunately fail to impress Penny's brutish ex-boyfriend. Afterwards, Koothrappali experiences the unexpected with a partygoer, Cheryl (ERIN ALLIN).

When Wolowitz seduces Penny's friend and ends up having sex with her in Penny's apartment, Penny sleeps on Leonard and Sheldon's couch. Meanwhile, with Wolowitz occupied, the guys discover that they are without a fourth member of their group. In desperation, they ask Penny to join one of their two-person Halo teams.

Koothrappali becomes overwhelmed when his parents arrange a blind date for him, but he discovers he actually can talk to a member of the opposite sex after a few drinks. However, complications arise when his beautiful date shows more interest in Sheldon.

Sheldon and Leonard are invited to present their joint findings at a physics conference, but Sheldon refuses. Penny steps in to mediate, but this only deepens the rift between the two best friends.

After hearing Penny sing, Leonard lies to avoid seeing her perform; Sheldon goes a step further. D.J. QUALL guest stars.

When Sheldon gets sick, the boys know what is in store for them and avoid him like the plague; this leaves an unsuspecting Penny to nurse the world's worst patient back to health.

When Leonard and Sheldon meet a teenage physics prodigy, Sheldon is distraught that the boy genius is younger and smarter, and crafts a plan to derail the young prodigy's research.

The guys kick Sheldon off the team for the Physics Bowl and enlist his nemesis Leslie Winkle (recurring guest star SARA GILBERT) to take his place.

When the guys buy a time-machine prop from a classic movie, Penny's reaction forces Leonard to take a hard look at his life.

Leonard, Wolowitz, and Koothrappali all become smitten with Sheldon's twin sister, Missy (guest star COURTNEY HENGGELER), but Sheldon declares he will decide whom his sister dates.

When Penny attempts to throw Leonard a wild surprise party, Sheldon gets in the way.

When Penny breaks up with her boyfriend, Leonard finally gets up the courage to ask her out on a date. When she says yes, each seeks the "wisdom" of Sheldon, a reluctant advisor.