Drake's Assault on Panama also known as the Defence of Panama was a military event that took place in January 1596 during the Anglo–Spanish War. An English expedition under the command of Francis Drake and Thomas Baskerville attacked the Spanish Main via Nombre de Dios in order to cross the isthmus of Panama. Ravaged with dysentery and other diseases the English were repelled and defeated. Drake would die of the former and the expedition was forced to retreat back to England all the while harassed by the Spanish.

Sir Francis Drake was an English explorer and privateer best known for his circumnavigation of the world in a single expedition between 1577 and 1580. This was the first English circumnavigation, and third circumnavigation overall. He is also known for participating in the early English slaving voyages of his cousin, Sir John Hawkins, and John Lovell. Having started as a simple seaman, in 1588 he was part of the fight against the Spanish Armada as a vice-admiral.