The southern chunk of Panama leading to the border with Colombia and stretching to both coasts is the Darién National Park. Home to the biggest rainforest in the Western Hemisphere outside of the Amazon Basin and the only gap in the Pan-American Highway, Darien is recommended really only for isolated travel to lodges or tourist-friendly communities. Many tourists try to cross through to Colombia, but this trek is very dangerous as armed Colombian insurgents hostile to travelers regularly cross into the area. Disease is also a serious problem here, especially during the rainy season from May to December.

The private Punta Patiño Nature Reserve is especially recommended for wildlife viewing and getting away from civilization. A variety of travel agencies in Panama City can help with booking a rain forest tour to this area.