Certain embodiments are directed to methods of ameliorating, treating, or preventing Kennedy's Disease in a subject carrying a mutation in the Androgen Receptor (AR) gene, such as expansion of a CAG trinucleotide repeat, which is associated with Kennedy's Disease, by administering an antisense compound targeted to AR. Several embodiments provided herein relate to the discovery that antisense compounds targeting Androgen Receptor can ameliorate, treat, or prevent Kennedy's Disease in a subject carrying a mutation in the Androgen Receptor gene, such as expansion of a CAG trinucleotide repeat, which is associated with Kennedy's Disease.