Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G (intramuscular or intravenous use) and penicillin V (given by mouth). Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

10% of the population claims penicillin allergies but because the frequency of positive skin test results decreases by 10% with each year of avoidance, 90% of these patients can tolerate penicillin. Additionally, those with penicillin allergies can usually tolerate cephalosporins (another group of β-lactam) because the Immunoglobulin E (IgE) cross-reactivity is only 3%.

Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming as a crude extract of P. rubens. Fleming's student Cecil George Paine was the first to successfully use penicillin to treat eye infection (Ophthalmia neonatorum) in 1930. The purified compound (penicillin F) was isolated in 1940 by a research team led by Howard Florey and Ernst Boris Chain at the University of Oxford. Fleming first used the purified penicillin to treat streptococcal meningitis in 1942. The 1945 Nobel Prize in Physiology or Medicine was shared by Chain, Fleming, and Florey.

Several semisynthetic penicillins are effective against a broader spectrum of bacteria: these include the antistaphylococcal penicillins, aminopenicillins, and antipseudomonal penicillins.