The Missouri River showed the expedition many different animals and beautiful land, but the journey also brought serious dangers. On May 14, 1805, between the Milk and Musselshell rivers in today's Montana, a huge grizzly bear charged a group of hunters, chased two men into the river, and was finally killed only after the men had shot it a total of eight times.

The white pirogue, a large river boat, carried many of the expedition's most valuable items, including important papers, scientific instruments, medicines, and trade goods. Strong winds funneled through the river's high cliffs and twisting bends could suddenly strike the boats and nearly tip them over, which made the captains very worried about losing their precious cargo.