Lithium as a chemical element was discovered nearly 200 years ago. Its introduction to the treatment of affective disorders at the end of the nineteenth century by Carl Lange in Denmark and, in the second half of the twentieth century, by John Cade in Australia was linked to studies on uric acid. Carl Georg Lange (1834–1900) is regarded as one of the most prominent Danish scientists of the nineteenth century. His achievements in neurology, psychology and psychiatry are still relevant today. He was a co-founder of a neurophysiological theory of emotions, known as the James–Lange theory. In 1886 he wrote a clinical treatise on periodic depression, in which he presented a biochemical theory that postulated the pathogenic role of an excess of uric acid in the brain. Based on this, he used lithium for the treatment of patients with depression. John Frederic Cade (1912–1980), to whom the introduction of lithium to contemporary psychiatry is owed, used lithium after experimenting with uric acid in guinea pigs. He was the first psychiatrist to give lithium to manic patients, with spectacular therapeutic effects. His paper, published in 1949 in “The Australian Journal of Psychiatry”, is regarded as a harbinger of modern psychopharmacology. In recent years, it has been demonstrated that uric acid and the associated purinergic system may play a role in the pathogenesis and treatment of affective disorders. A purinergic hypothesis of affective disorders is presented in this study, assuming a significant pathogenic role for uric acid, adenosine receptors P1 and nucleotide receptors P2X and P2Y.