Viruses come in three colors: Red (Fever, which causes heat), Blue (Chill, which can manipulate the cold), and Yellow (Weird, which can morph people into different shapes or species). To defeat a Virus, Dr. Mario must line up three Megavitamins of the same color next to the Virus of that color. The Virus, along with the Megavitamins, will then disappear. After clearing one jar of Viruses, Dr. Mario will move to the next one, with each jar containing increasingly more Viruses.
 Dr. Mario series
 Dr. Mario
Viruses first appeared in the NES and Game Boy game Dr. Mario, where they are small germs that Dr. Mario must eliminate. To do this, he uses Megavitamins, which can come in combinations of their colors (Red, Blue and Yellow), Four of these Megavitamins must be stacked on top of a virus of the same color to eliminate it. As the difficulty increases, the number of viruses also increase.
In the Game Boy version due to the system being incapable of displaying bright colors, Viruses appear in Black, White and Grey. The White virus resembles the Yellow virus, but the Black and Grey virus look different from the Red and Blue virus.
 Dr. Mario 64
Viruses appears again in Dr. Mario 64, and they play the same role as before. The way to beat them stays the same too.
 Dr. Mario Online Rx
 Nintendo Comics System
The Viruses appeared as the main antagonists in Nintendo Comics System's adaptation of Dr. Mario entitled "The Doctor Is In... Over His Head". It was this appearance that named the Red Virus Fever, the Blue Virus Chill, and the Yellow Virus Weird.
In the same episode, the Viruses are given special powers: Chill can manipulate the cold, Fever can control heat, and Weird can forcibly morph others into different shapes and creatures.
 Club Nintendo
 WarioWare series
In WarioWare, Inc.: Mega Microgame$!, one of 9-Volt's microgames called Dr. Mario is based on the game Dr. Mario, and the player must defeat the Viruses using Megavitamins, just like in the game. There is also a minigame in the same game called Dr. Wario, which is a Wario version of Dr. Mario, where the Viruses look different. In WarioWare: Twisted! in the microgame Weird Science, a blue Virus makes an appearance.
 Mario & Luigi series
 Mario & Luigi: Superstar Saga
Viruses also appear in Mario & Luigi: Superstar Saga. In this game, Viruses roam the halls of Woohoo Hooniversity, Cackletta's temporary base-of-operations. Viruses appear in all three colors and attack in groups. However, in this game, Viruses can change color. In fact, when hit by Mario or Luigi, a Virus will assume a different color. When all the current Viruses in-battle match in color, they will be instantly destroyed, somewhat similar to the way they are defeated in Dr. Mario.
 Mario & Luigi: Bowser's Inside Story
The Blue Virus makes a minor cameo in Mario & Luigi: Bowser's Inside Story. After knocking out all the body segments of a Toothy, the Toothy attacks by spitting out a Blue Virus holding a spear to attack the player.
In the Toadley Clinic's lobby, there is a sign on the wall that shows a blue Virus in a red circle with a "/" through it (similar to a "no smoking" or "no pets" sign).
 Mario & Luigi: Dream Team
Viruses appear in Mario & Luigi: Dream Team as enemies. In the field, Viruses chase Mario and Luigi upon sight. Viruses also change color whenever they are damaged (with the exception of counter-attacks); much like how they did in Mario & Luigi: Superstar Saga. The pattern they go in is from blue to yellow to red and back to blue again, repeating itself. The player can connect three or more of the same color to make them disappear, defeating the connected Viruses instantly, also like in Mario & Luigi: Superstar Saga. If a Virus is defeated, the ones behind it will move forward to the front if possible. They always appear in a group of 16, which is the most enemies seen in a battle in the real world. They are also one of the very few enemies who can inflict the Mini status on the Bros. which decreases their Attack and Defense and shrinks them.
Viruses may attack by forming two lines, one in the foreground and one in the background, and proceeding to move several steps in any direction each time. This can be dodged by jumping when appropriate. Viruses may also attack by circling the Bros. in a single file line, Mario and Luigi then having to hammer them all into a pile before they attack them after circling several times. If three of the same colour land on the pile consecutively, they disappear like they would normally.
 Mario Kart series
 Mario Kart Arcade GP
 Nintendo Puzzle Collection
The Viruses reappeared in the Dr. Mario game (a close remake of Dr. Mario 64) of Nintendo Puzzle Collection.
 Official Profiles and Statistics
 Trophy Information from Super Smash Bros. Melee
 Sticker Information from Super Smash Bros. Brawl