This review outlines factors that differentiate botulinum toxin serotypes and focuses on the unique features of the commercially available form of BoNT-B (i.e., Myobloc/NeuroBloc). A series of preclinical studies in Cynomolgus monkeys are reviewed. Each of these studies used electrophysiologic measures of changes in the compound muscle action potential (CMAP) following supramaximal nerve stimulation to evaluate the direct effects of the toxin in the injected muscle, as well as the spread of the effects to non-injected muscles. The results of 14 studies were summarized, including several that compared the effects of equivalent doses of BoNT-A and BoNT-B injected into muscles on the opposite side of the same monkey. There is clear evidence that when equivalent doses of BoNT-A and BoNT-B are assessed, there is greater spread to both nearby and remote non-injected muscles associated with BoNT-A. Similar studies in the mouse model demonstrated that high, but non-lethal, doses of BoNT-A unilaterally injected into the foot resulted in spread of the effects across the midline to the opposite non-treated foot, while there was no evidence of bilateral effects with equivalent unilateral injections of BoNT-B. Finally, this review summarizes a series of studies in the trapezius and gastrocnemius muscles of monkeys demonstrating that when doses producing equivalent initial effects of BoNT-A and BoNT-B are compared, the duration of effects and the time course of recovery are almost identical across toxins.