Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain hypersecretory disorders, including hyperhidrosis, sialorrhea, and chronic rhinorrhea, an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations for each therapeutic indication, based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of axillary hyperhidrosis in a total of 923 patients, the evidence supported a Level A recommendation for BoNT-A, with a Level B recommendation for A/Abo and A/Ona and a Level U recommendation (insufficient data) for A/Inco and B/Rima. Five trials in 82 patients supported the use of BoNT in palmar hyperhidrosis, with a Level B recommendation for BoNT-A and a Level C recommendation for BoNT-B; individual formulations received a Level U rating due to insufficient data. BoNT (and all individual formulations) received a Level U recommendation for the treatment of gustatory sweating. Support for use of BoNT in sialorrhea was derived from eight trials in a total of 222 adults and children. Evidence supported a Level B recommendation for A/Abo, A/Ona, and B/Rima and a Level U recommendation for A/Inco. Evidence supported a Level B recommendation for A/Ona for the treatment of allergic rhinitis, based on two Class II studies in 73 patients. A lack of published studies for A/Abo, A/Inco, or B/Rima supported a Level U recommendation for those formulations. Further clarity on the optimal mode of administration and additional studies using other BoNT formulations are needed to fill current evidence gaps.