Kennedy’s disease, also known as spinal and muscular atrophy (SBMA), is a type of motor neurone disease caused by the expansion of a CAG repeat sequence within the androgen receptor (AR) gene.  This sequence encodes a polyglutamine tract within the translated protein, and induces neurodegeneration when numbering greater than 40.  The phenotype in Kennedy’s disease results from the degeneration of lower motor neurones in the brain stem and spinal cord.  The AR gene is located on the X-chromosome, and only males carrying this mutation develop significant features of the disease.  It was therefore believed that Kennedy’s disease was a recessive condition, presenting in males with one copy of the mutant allele.  It is now known that females escape the manifestations of Kennedy’s disease not because it is a recessive X-linked trait, but because the neurodegenerative processes in Kennedy’s disease are triggered by the binding of androgens to the AR.  Females carrying the mutant Kennedy’s allele are therefore protected from developing the disease by their lower levels of circulating androgens.  The AR is a ligand-dependent nuclear transcription factor which, in its unliganded state, resides predominantly in the cytoplasm, whereas after ligand binding, the dimerised ligand-receptor complex translocates to the nucleus.  Evidence to date suggests that the nucleus is the cellular compartment where polyglutamine expanded proteins exert their toxic effects on susceptible neurones. The evidence supporting a crucial role for androgens in the pathogenesis of Kennedy’s disease is becoming more compelling.  This discovery has been central to understanding some of the mechanisms contributing to the pathogenesis of this disease and provides an avenue for hormonal manipulation as a potential therapeutic approach.  Given that one of the manifestations of this disease is mild androgen insensitivity, which presents clinically as gynaecomastia and reduced fertility, clinicians initially believed that sufferers of Kennedy’s disease would benefit from androgen treatment that aimed at overcoming their apparent loss of receptor function.  However, based on recent evidence, we postulate that androgens are more likely to exacerbate the features of the disease than improve them. In this review, we discuss the evidence surrounding the role of androgens in Kennedy’s disease, including current studies in animal models and how this may impact on future therapeutic approaches.