The decision to prescribe long-term or 'life-long' antibiotics in patients requires careful consideration by the treating clinician. While several guidelines exist to help assist in this decision, the long-term consequences are yet to be well studied. In this review, we aim to provide a summary of the available evidence for patient populations where long-term antibiotic therapy is currently recommended in clinical practice. We will also discuss the pitfalls of this approach, including medication adverse effects, economic cost and any possible contribution to the emerging epidemic of microbial resistance.