Trail hikers who attempt to complete the entire trail in a single season are called "thru-hikers"; those who traverse the trail during a series of separate trips are known as "section-hikers". Rugged terrain and cold weather during the spring and fall make thru-hiking difficult. Only about 30% of those who make the attempt report to the Appalachian Trail Conservancy that they completed it; 2007 estimates said 28,500 have done so. It is widely acknowledged that many or even most of these have skipped portions of the Trail. Completion generally requires five to seven months, although some have done it in three months, and several trail runners have completed the trail in less time. Trail runners typically tackle the AT with automobile support teams, without backpacks, and without camping in the woods.

The current unofficial speed record for through-hiking the AT was set by trail runner Andrew Thompson in 2005, at 47 days, 13 hours and 31 minutes. Thompson made the trip southbound, from late June to early August.

Thru-hikers are classified into many informal groups. "Purists" are hikers who stick to the official AT trail except for side trips to shelters and camp sites. "Blue Blazers" cut miles from the full route by taking side trails marked by blue blazes. The generally pejorative name "Yellow Blazers," a reference to yellow road stripes, is given to those who hitchhike to move down the trail. There are also those who hike the trail in sections known as "sectioners" as opposed to those who hike the whole trail as one course.

Most thru-hikers walk northward from Georgia to Maine, and generally start out in early spring and follow the warm weather as it moves north. These "north-bounders" are also called NOBO (Northbound) or GAME (Georgia (GA)-to-Maine (ME)), while those heading in the opposite direction are termed "south-bounders" (also SOBO or MEGA).

Part of hiker subculture includes making colorful entries in logbooks at trail shelters, signed using trail names.

The Appalachian Trail Conservancy gives the name "2000 Miler" to anyone who completes the entire Trail. The ATC's recognition policy for "2000 Milers" gives equal recognition to thru-hikers and section-hikers, operates on the honor system, and recognizes blue-blazed trails or officially required road walks as substitutes for the official, white-blazed route during an emergency such as a flood, forest fire, or impending storm on an exposed, high-elevation stretch.