L-arginine was first isolated in 1886. In 1932, scientists learned that L-arginine is needed to create urea, a waste product that is necessary for toxic ammonia to be removed from the body. In 1939, researchers discovered that L-arginine is also needed to make creatine. Creatine breaks down into creatinine at a constant rate, and it is cleared from the body by the kidneys.

Arginine is considered a semi-essential amino acid because even though the body normally makes enough of it, supplementation is sometimes needed. For example, people with protein malnutrition, excessive ammonia production, excessive lysine intake, burns, infections, peritoneal dialysis, rapid growth, urea synthesis disorders, or sepsis may not have enough arginine. Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver.

Arginine changes into nitric oxide, which causes blood vessel relaxation (vasodilation). Early evidence suggests that arginine may help treat medical conditions that improve with vasodilation, such as chest pain, clogged arteries (called atherosclerosis), coronary artery disease, erectile dysfunction, heart failure, intermittent claudication/peripheral vascular disease, and blood vessel swelling that causes headaches (vascular headaches). Arginine also triggers the body to make protein and has been studied for wound healing, bodybuilding, enhancement of sperm production (spermatogenesis), and prevention of wasting in people with critical illnesses.