Substituted amphetamines, or simply amphetamines, are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with substituents. The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Examples of substituted amphetamines are amphetamine (itself), methamphetamine, ephedrine, cathinone, phentermine, mephentermine, tranylcypromine, bupropion, methoxyphenamine, selegiline, amfepramone (diethylpropion), pyrovalerone, MDMA (ecstasy), and DOM (STP).

Some of amphetamine's substituted derivatives occur in nature, for example in the leaves of Ephedra and khat plants. Amphetamine was first produced at the end of the 19th century. By the 1930s, amphetamine and some of its derivative compounds found use as decongestants in the symptomatic treatment of colds and also occasionally as psychoactive agents. Their effects on the central nervous system are diverse, but can be summarized by three overlapping types of activity: psychoanaleptic, hallucinogenic and empathogenic. Various substituted amphetamines may cause these actions either separately or in combination.

A variety of prodrugs of amphetamine and/or methamphetamine exist, and include amfecloral, amfetaminil, benzphetamine, clobenzorex, D-deprenyl, deprenyl, dimethylamphetamine, ethylamphetamine, fencamine, fenethylline, fenproporex, furfenorex, lisdexamfetamine, mefenorex, prenylamine, and selegiline.

There is almost an excessive amount of Prodrugs in the substituted amphetamine class. For example, Benzphetamine^{[circular reference]} is a prodrug for both Dextroamphetamine and Dextromethamphetamine.

A number of synthetic Russian amphetamine derivatives have been developed, including alafen (amphetamine–β-alanine), feprosidnine, gamofen (amphetamine–GABA), mesocarb, methylphenatine, pabofen (amphetamine–PABA), phenatine (amphetamine–niacin; N-nicotinoylamphetamine), phenylphenamine (phenylamphetamine), propylphenamine (propylamphetamine), pyridoxiphen (amphetamine–pyridoxine), and thiophenatine (N-thionicotinoylamphetamine).

Amphetamines are a subgroup of the substituted phenethylamine class of compounds. Substitution of hydrogen atoms results in a large class of compounds. Typical reaction is substitution by methyl and sometimes ethyl groups at the amine and phenyl sites:

Ephedra was used 5000 years ago in China as a medicinal plant; its active ingredients are alkaloids ephedrine, pseudoephedrine, norephedrine (phenylpropanolamine) and norpseudoephedrine (cathine). Natives of Yemen and Ethiopia have a long tradition of chewing khat leaves to achieve a stimulating effect. The active substances of khat are cathinone and, to a lesser extent, cathine.

Amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu, although its pharmacological effects remained unknown until the 1930s. MDMA was produced in 1912 (in 1914, according to other sources) as an intermediate product. However, this synthesis also went largely unnoticed. In the 1920s, both methamphetamine and the dextrorotatory optical isomer of amphetamine, dextroamphetamine, were synthesized. This synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat asthma extracted exclusively from natural sources. Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French (now part of GlaxoSmithKline), as a medicine (Benzedrine) for colds and nasal congestion. Subsequently, amphetamine was used in the treatment of narcolepsy, obesity, hay fever, orthostatic hypotension, epilepsy, Parkinson's disease, alcoholism and migraine. The "reinforcing" effects of substituted amphetamines were quickly discovered, and the misuse of substituted amphetamines had been noted as far back as 1936.