Many episodes contain full male and female nudity. Particular episodes with strong sexualised nudity (and in some cases, obscured real sex) are "Sex, Sex, Sex", "The War on Porn", "Prostitution", "Yoga and Tantric Sex" and "Orgasms".

Frequent strong sex references throughout.

Mild slapstick violence between Penn and Teller.

In the "PETA" episode, there is some video footage of animal abuse, chickens being slaughtered, as well as footage of vandals breaking into animal research centres.

References and footage of famous violent events (eg. 9/11, JFK) appear in a few episodes, notably "Ground Zero" and "Conspiracy Theories".

Circumcision is seen in the episode "Circumcision".

The "Violent Video Games" contains simulated blood and dismemberment.

Consistent use of strong language (e.g. "fuck", "shit" and derivatives), and there are a few episodes with very strong language (e.g. "cunt" and derivatives). Notable episodes that include very strong language are "Profanity" and "The War On Porn".

A reason frequent strong language is used is cited in the first episode of the series: it is mainly to avoid being sued.

One episode is about The War on Drugs, called "The War On Drugs". Some scenes involving drug use are shown.

Infrequent mild references to drugs elsewhere.

While the show is generally light-hearted, some episodes shift tones throughout and can be intense. Ones of note include "Old People" and "Cheerleading". Some episodes (like "The Death Penalty", "Curcumcision" and "Ground Zero") are usually quite dark, and are more serious.

The episode "PETA" shows footage of animal abuse used by PETA, footage of convicted arsonist Rodney Coronado showing students at American University how to create molotov cocktails, and scenes where PETA compare The Holocaust to battery farming (all of which are heavily condemned and are portrayed negatively).