The premise of the episode (Monk taking a medication that turns him into someone that is the opposite of his normal self) parodies the plot of The Mask (a man who considers himself a loser puts on a mask that turns him into something that is the opposite of his normal self). In fact, several lines in "Mr. Monk Takes His Medicine" are taken directly from The Mask. For example: At the end of The Mask, a man and a woman are standing together and the man asks, "Are you sure you want to throw this away? Because once you do, you'll never see The Mask again," and the woman responds by throwing the mask away. These lines are spoofed at the end of "Mr. Monk Takes His Medicine." Monk mentions to Sharona, "You understand that if I throw these out, you'll never see The Monk again." Then he throws the pills in a garbage dumpster.