Orochimaru commonly uses cursed seals on his most powerful followers. To apply a cursed seal, Orochimaru needs to actually bite his intended target. Because he has sharp fangs and an extendable neck, this is a relatively simple task. The seal then appears somewhere on the user's body, and they subsequently lose consciousness. Sometime later, should they survive, they will awaken with the first level of the seal active and more than likely somewhat enraged. The seals work by forcibly drawing chakra from the user's body, giving the user a chakra capacity beyond what they would normally be capable of when active, as well as increased physical performance as a result of the increased chakra capacity.

The seals have two different levels, which can be determined by their appearance on the user. When inactive, the seal will simply be a black tattoo somewhere on the user's body. Orochimaru has a wide array of cursed seals, so the appearance of the seal will usually vary from user to user. Each seal always has three identical marks arranged in a circular pattern. When first activated, the marks on the seal glow and replicate, spreading over the user's body. This is known as the first level of the seal. The degree to which this occurs is dependent on the user, and the degree to which it spreads is proportionate to the overall effect it has. The second and final level of the seal causes the black marks to completely envelop the user. This is followed by an unnatural alteration of the user's body, with the only common features being yellow eyes with a black sclera (Sasuke's Sharingan is an exception). When in this level, the seal eats away at the user's personality, driving them to madness if used too long. It also takes quite a toll on their body, since they are being mutated by the seal.

Because the seals forcibly draw chakra from the user, they will often kill the user when first applied. Orochimaru has averaged a ten-percent success rate when applying these seals. Additionally, even if the user survives, their body will not be able to easily control the power the seals give them. To compensate for this, Orochimaru developed the Seishingan drug. The drug forces the user's body to become accustomed to the unnatural increase in power, but also kills the one who takes it. The Four Black Fog Formation Seal technique is used to keep the drug from killing the user by placing them in a temporary death state. Though Sound Four were the ones to perform the technique, it stands to reason that they weren't the ones that created it.

Orochimaru developed the cursed seals through experimentation on a prisoner named Jugo, whose body naturally produces an enzyme that triggers a state similar to the cursed seal. The difference between Orochimaru's seals and the unrefined enzyme are the effect they have: while the cursed seal is controllable, the unrefined enzyme produces uncontrollable rage in those exposed to it, including Jugo himself, and the effects cannot be controlled.

Name: Ten no Juin, literally "Cursed Seal of Heaven"
Wearers: Sasuke Uchiha, Anko Mitarashi

The counterpart of the Cursed Seal of Heaven, this seal was given to Kimimaro by Orochimaru in the hope that he might one day become his next host. Unfortunately for the both of them, Kimimaro contracted a fatal disease. The seal consists of three slightly curved lines, which spread in a square pattern. When the second level of the seal is active, Kimimaro takes on a dinosaur-like appearance, complete with a tail. Several large bones also protrude from his skin, and his skin becomes dark brownish-maroon.

Tayuya's cursed seal consists of three hooks, similar to a triskelion. When the second level of her seal is active, her hair grows longer, she grows five oddly-placed horns, and her skin turns dark brown. The horns grow when she exerts herself.

After stealing the necessary ingredients from the Nara clan's medical laboratory, Mizuki created the potion and drank it. This increased his musculature, caused three tiger-like stripes to appear on his arms, and increased his physical attributes in much the same manner as a cursed seal. Additionally, he was able to channel all of his chakra into strength and the energy changed his appearance to resemble a tiger's. As a side effect of focusing all his chakra on strength, his speed decreased dramatically.

Though quite effective, Orochimaru neglected to tell Mizuki that the potion was so far incomplete, drinking it burned up all the energy in Mizuki's cells, leaving him a withered husk of a person. This would have killed him in normal circumstances, but Tsunade's medical expertise saved him from what would otherwise have meant his death. Unfortunately for Mizuki, the damage caused left him unable to ever continue his life as a ninja.