This documentary film follows the professional and private lives of the 2004 U.S. Wheelchair Rugby team. Murderball is a highly engaging, informative look at the lives of a group of quadriplegic men who are also elite athletes. The sport of "murderball" combines basketball, hockey, and rugby. It is played in custom-built wheelchairs with angled, shield-like metal side plates that make the chairs look like chariots, encouraging the term "gladiators" that is often applied to the players. Invented in Canada in the 1970s, murderball was renamed "wheelchair rugby" or "quad rugby" to make it less offensive to corporate sponsors, but retains its toughness with any name. The sport is played without helmets, and its players tackle each other through chair-to-chair collisions as they try to move the ball to the end zones.

The documentary begins with the 2002 World Wheelchair Rugby Championships in Sweden, includes team tryouts and competitions with arch-rival Canada, and closes with the Paralympic Games (held two weeks after the traditional Olympic Games end) in Athens, Greece. The film is a fast-paced sports documentary with abundant chair-level footage of action on the court, but also focuses on many aspects of the personal lives of key players, including psychological conflicts and sexuality. While the documentary is focused on the entire team, not individuals, three distinct subplots include the emotional journey of team captain Mark Zupan, including his relationship with the friend whose actions precipitated Zupan's disabling accident over ten years earlier; the passion and resentment of the Canadian team coach Joe Soares, who was cut from the U.S. Team and whose obsession with murderball leaves little space for Soares to appreciate his musically gifted teenage son until his own heart attack; and the experiences of newly disabled athlete Keith Cavill.