Tamoxifen is a selective oestrogen receptor modulator (SERM) with an established role in the treatment and chemoprevention of hormone-related breast cancer. It is also cardioprotective and increases bone mineral density. However, due to pleiotrophic ligand-receptor properties, its role in a variety of seemingly unrelated disorders, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, systemic lupus erythematosus and urological cancers, has been investigated in many studies. The non-patented drug tamoxifen confers a significant advantage over newer drugs in being inexpensive and well-tolerated with a known side-effect profile. This review highlights the interaction of tamoxifen on oestrogen receptors (ERs) and assesses whether this agent continues to have future applications in a variety of clinical settings, both as a therapy in early and established disease and usage as a prophylactic in those at risk of debilitating conditions. Indeed, it may have as-yet-unknown benefit(s) in a variety of conditions, both as a prophylactic in those at high-risk and also as in novel therapeutic strategies in established disease. Future clinical studies may seek to establish the exact future role and efficacy for SERMs both in men and women. Perhaps a multi-functional SERM such as tamoxifen may be the aspirin of the 21[sup]st century.