Reserpine, an alkaloid of the Rauwolfia serpentina plant isolated during the middle of the 20th Century, represented a highly important clinical advance in the treatment of schizophrenia whose pharmacological tools were limited to chlorpromazine that was introduced in the clinical area two years before. Both agents would come into the history as the drugs that made possible the beginning of the psychopharmacological era. In the present article, a revision is made of the complicated process leading to the isolation and synthesis of reserpine, by the Swiss pharmaceutical company Ciba (Schlittler and Müller) and how its pharmacological properties (Bein) were discovered and studied, in the animals laboratory, mainly, the "tranquillizers". The introduction of this antipsychotic in psychiatry, which was initiated in 1954 (half a century ago), and the results obtained in the first clinical studies, as well as the role played by researchers such as Kline, Delay, Noce, Hollister, Altschule, etc. are then described. In addition, and from a historical perspective, the discovery of the adverse effects of this drug, especially those of extrapyramidal nature (dyskinesia and akathisia), are studied, concluding with the reasons that produced its rapid clinical decline, among which the genesis of depressive pictures (phenomenon presently questioned) may be emphasized. Finally, the conclusion reached was that, although the clinical relevance of reserpine was not as evident and long lasting as chlorpromazine, its initial contribution to the treatment of schizophrenic patients was of maximum importance.