The usual route for medical use is oral administration. In recreational use, it can be swallowed, snorted, smoked, dissolved in water and injected (or even without water, in what is called a dry shot), inserted anally (with or without dissolution in water; also known as a booty bump), or into the urethra. The potential for addiction is greater when it is delivered by methods that cause the concentration in the blood to rise quickly, principally because the effects desired by the user are felt more quickly and with a higher intensity than through a moderated delivery mechanism. Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate that the blood level of the drug increases. In general, smoking is the fastest mechanism (i.e., it causes the blood concentration to rise the most quickly in the shortest period of time as it allows the substance to travel to the brain through a more direct route than intravenous injection), followed by injecting, anal insertion, insufflation and swallowing.

"Smoking" methamphetamine actually refers to vaporizing it to produce fumes, rather than burning and inhaling the resulting smoke, as with tobacco. It is commonly smoked in glass pipes, or in aluminum foil heated by a flame underneath. This method is also known as "chasing the white dragon" (as derived from the method of smoking heroin known as "chasing the dragon"). There is little evidence that methamphetamine inhalation results in greater toxicity than any other route of administration. Lung damage has been reported with long-term use, but manifests in forms independent of route (pulmonary hypertension and associated complications), or limited to injection users (pulmonary emboli).

Injection is a popular method for use, but carries quite serious risks. The hydrochloride salt of methamphetamine is soluble in water; injection users may use any dose from 125 mg to over a gram, using a small needle. This dosage range may be fatal to non-addicts; addicts rapidly develop tolerance to the drug. Injection users often experience skin rashes (sometimes called "speed bumps") and infections at the site of injection. As with any injected drug, if a group of users shares a common needle or any type of injecting equipment without sterilization procedures, blood-borne diseases such as HIV or hepatitis can be transmitted as well.

Very little research has focused on anal insertion as a method, and anecdotal evidence of its effects is infrequently discussed, possibly due to social taboos in many cultures regarding the anus. This is often known within communities that use meth for sexual stimulation as a "booty bump," "keistering," or "plugging," and is anecdotally reported to increase sexual pleasure while the effects of the drug last.