Abstract The neuromuscular junction (NMJ) is a critical component of the motor unit that is made up of the distal, unmyelinated nerve terminal, synaptic space, and end-plate region of the muscle fiber. Contraction of muscle fiber involves a coordinated series of steps that ultimately generates an action potential at the muscle end plate (also known as an end-plate potential). Normally the end-plate potential substantially exceeds the threshold necessary to trigger an action potential in the muscle fiber, and this difference is termed the safety factor of neuromuscular transmission. Disorders that affect the NMJ reduce this safety factor, a change that results in fatigable weakness.