The legendary Mississippi flows north to south through the middle of America, and is the fourth largest river in the world. In its lower reaches it passes through sleepy river towns, Southern cities, and plenty of Civil War history. Cruises are available virtually year-round, and include experiences on classic-style steamboats that explore the stretch between New Orleans and the "Blues City" of Memphis, or run round-trip from New Orleans. The route brings you to antebellum mansions and places like Natchez, oozing Southern charm. You'll want to spend time in both the "Big Easy" and Memphis, where attractions include the National Civil Rights Museum and Elvis's Graceland. Other highlights en route include Oak Alley Plantation, which looks straight out of "Gone With the Wind," and the Civil War battlefields at Vicksburg National Military Park. There are also river-side casinos in several places.

Exploring between St. Louis and St. Paul, these cruises visit several states and appeal to those who want to get a good look at the heartland. Scenery includes dense foliage, open prairies, and limestone cliffs, with three national parks in the picture. There are also historic river towns, along with plenty of Mark Twain lore. This stretch is loaded with locks, and cruises are offered only between July and October (the fall itineraries bringing a spectacular display of colors). Highlights include Hannibal, Missouri, birthplace of Samuel Clemens (Mark Twain); the Mark Twain Caves, where the legendary author explored as a kid; and, of course, the stunning St. Louis Gateway Arch, towering over the Mississippi. Along the way you’ll also find opportunities to take the unusual funicular railway in Dubuque, Iowa, to check out the brewery scene in La Crosse, Wisconsin, and to purchase artisan ceramics in Red Wing, Minnesota.

Less common summertime cruises explore Mississippi River tributaries like the Ohio River between Memphis and Cincinnati. Visit John James Audubon's hometown of Henderson, Kentucky, and stop by Louisville for popular sights like Churchill Downs Racetrack and the Kentucky Derby Museum. There are also occasional cruises between St. Louis and Cincinnati, which put the emphasis on Kentucky's Bourbon Trail.

Especially popular during peak foliage season, Hudson River cruises typically run round-trip between New York City and Albany, which is almost a straight shot north. Weeklong cruises stops each day at a different historic riverfront town (Kingston, Sleepy Hollow) to see sites like the Vanderbilt Mansion and the Franklin D. Roosevelt Presidential Library and Museum near Poughkeepsie. Many prominent families had mansions along the river that are now open to visitors; besides the Vanderbilts, the Rockefellers had Kykuit, while Lyndhurst is one of the most elaborate Gothic revival mansions in the U.S. (it was built for a NYC mayor). Since the cruises start and end in Manhattan, you'll also have a chance to check out the urban foliage in Central Park, as well as plenty of other city sights.

The largest river in the Pacific Northwest, the scenic Columbia River flows south from Canada, dividing Oregon and Washington. Cruises explore the border between the states, together with a portion of the Snake River towards Idaho. Natural beauty is the big reason to cruise here. Itineraries offered spring to fall take you through the breathtaking Columbia River Gorge and give you access to such sights as Hells Canyon and Multnomah Falls. Along the way you'll hear much about explorers Lewis and Clark as you trace some of their western route, and also catch up on the area's vibrant Native American history. Drinking locally produced wine and tasting freshly caught salmon and crab is part of the scene, too. The cruises are between Oregon's über-hip Portland and the quaint small Washington town of Clarkston (named for Clark), which is across the Snake River from Lewiston (named for Lewis), Idaho.