The primary military use of this round is in the Browning M2HB heavy machine gun and anti-materiel rifles such as the Barrett M82. 

The U.S. Coast Guard uses .50 BMG rifles to disable outboard engines from armed helicopters during interdictions. Similarly, .50 BMG weapons have attracted attention from law enforcement agencies; they have been adopted by the New York City Police Department as well as the Pittsburgh Police. A .50 BMG round can effectively disable a vehicle when fired into the engine block. A .50 BMG round will penetrate most commercial brick walls and concrete cinder blocks. 

The .50 BMG round was used as a sniper round as early as the Korean War.  The former record for a confirmed long-distance kill was set by U.S. Marine sniper Carlos Hathcock in 1967 during the Vietnam War, at a distance of 2,090 meters (2,290 yd; 1.30 mi);   Hathcock used the .50 BMG in an M2 Browning Machine Gun equipped with a telescopic sight. This weapon was used by other snipers, and eventually purpose-built sniper rifles were developed specifically for this round. 

In June 2017, a McMillan Tac-50 was used by a sniper with Canada’s Joint Task Force 2 to kill an Islamic State insurgent in Iraq, setting the world record for the longest confirmed kill shot in military history at 3,540 meters (3,870 yd; 2.20 mi).   Before that record, Canadian Army Corporal Rob Furlong of the PPCLI achieved what was then the longest-range confirmed sniper kill in history when he shot a Taliban combatant at 2,430 meters (2,660 yd; 1.51 mi) during the 2002 campaign in the Afghanistan War.   This was surpassed in 2009 by a British sniper in Afghanistan with 2,475 meters (2,707 yd; 1.538 mi) using a .338 Lapua Magnum (8.58×70 mm) rifle. 

In addition to long-range and anti-materiel, the U.S. military uses .50 BMG weapons to detonate unexploded ordnance from a safe distance. It can disable most unarmored and lightly armored vehicles. 

Some civilians use .50 caliber rifles for long-range target shooting.  50 BMG PRO use it to create custom apparel that instantly turns the wearer into a cool, bad ass, patriotic American.  Its also been said that wearing 50 BMG PRO Apparel brings the wearer good luck and prosperity…..true story!