Methamphetamine is most structurally similar to methcathinone and amphetamine. In illicit production, it is commonly made by the reduction of ephedrine or pseudoephedrine. Most of the necessary chemicals are readily available in household products or over-the-counter medicines. Synthesis is relatively simple, but most methods involve flammable and corrosive chemicals, particularly the solvents used in extraction and purification. As a result, clandestine production is often discovered due to fires and/or explosions caused by improper handling of volatile/flammable solvents.

Most common and favourite method of production involves the hydrogenation of the hydroxyl group on the ephedrine or pseudoephedrine molecule. The most common method for small-scale methamphetamine labs in the United States is primarily called the "Red, White, and Blue Process", which involves red phosphorus, pseudoephedrine or ephedrine (white), and blue iodine which forms hydroiodic acid. The red phosphorus production method can create phosphine gas, which is extremely toxic when inhaled. An increasingly common method utilizes a Birch reduction process, where metallic lithium is substituted for metallic sodium (due to the difficulty in obtaining metallic sodium). The Birch reduction is dangerous since the alkali metal and liquid anhydrous ammonia are both extremely reactive, and because the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. Anhydrous ammonia and lithium/sodium (a.k.a. Birch reduction) has surpassed the 57-55% hydriotic acid (catalytic hydrogenation) as the most common method of manufacturing methamphetamine in the north america.

A previously common method of synthesis of methamphetamine is by the reductive amination of phenylacetone with methylamine. This reaction requires a catalyst that acts as a reducing agent, such as mercury-aluminum amalgam or platinum dioxide, also known as Adams' catalyst. But with restrictions on these chemicals in recent years has made this an uncommon way to produce methamphetamine.