The history of mining and exploration in Panama is a case study of the evolution of mining in a tropical, island arc environment in the New World from prehistoric to modern times over a period of ~1900 years. Panama has a strong mineral endowment of gold (~984 t), and copper (~32 Mt) resulting in a rich mining heritage. The mining history can be divided into five periods. The first was the pre-Columbian period of gold mining from near the start of the Current Era at ~100 CE to 1501, following the introduced of gold metalwork fully fledged from Colombia. Mining of gold took place from placer and vein deposits in the Veraguas, Coclé, Northern Darien and Darien goldfields, together with copper for alloying. Panama was the first country on the mainland of the Americas to be mined by Europeans during the Spanish colonial period from 1501-1821. The pattern of gold rushes, conquest and settlement can be mapped from Spanish records, starting in Northern Darien then moving west to Panama in 1519 and Nata in 1522. From here, expeditions set out throughout Veraguas over the next century to the Veraguas (Concepción), Southern Veraguas, Coclé and Central Veraguas goldfields. Attention returned to Darien in ~1665 and led to the discovery of the Espíritu Santo de Cana gold mine, the most important gold mine to that date in the Americas. The third period was the Republican period following independence from Spain in 1821 to become part of the Gran Colombia alliance, and the formation of the Republic of Panama in 1903. This period up to ~1942 was characterized by mining of gold veins and placers, and manganese mining from 1871. Gold mining ceased during World War Two. The fourth period was the era of porphyry copper discoveries and systematic, regional geochemical exploration programs from 1956 to 1982, carried out mainly by the United Nations and the Panamanian government, as well as private enterprise. This resulted in the discovery of the giant porphyry copper deposits at Cerro Colorado (1957) and Petaquilla (Cobre Panama, 1968), as well as several other porphyry deposits, epithermal gold deposits and bauxite deposits. The exploration techniques for the discovery of copper were stream sediment and soil sampling, followed rapidly by drilling. The only mine developed in this period was marine black sands for iron ore (1971-1972). The fifth and current period is the exploration and development of modern gold and copper mines since 1985 by national and foreign companies, which started in response to the gold price rise. The main discovery methods for gold, which was not analyzed in the stream sediment surveys, were lithogeochemistry of alteration zones and reexamination of old mines. Gold mines were developed at Remance (1990-1998), Santa Rosa (1995-1999 with restart planned in 2020) and Molejon (2009-2014), and the Cobre Panama copper deposit started production in 2019. The level of exploration in the country is still immature and there is high potential for the discovery of new deposits.