Antibiotics are essential agents that have greatly reduced human mortality due to infectious diseases. Their use, and sometimes overuse, have increased over the past several decades in humans, veterinary medicine and agriculture. However, the emergence of resistant pathogens is becoming an increasing problem that could result in the re-emergence of infectious diseases. Antibiotic prescription in human medicine plays a key role in this phenomenon. Under selection pressure, resistance can emerge in the commensal flora of treated individuals and disseminate to others. However, even if the effects of antimicrobial use on resistance is intuitively accepted, scientific rationales are required to convince physicians, legislators and public opinion to adopt appropriate behaviours and policies. With this review, we aim to provide an overview of different epidemiological study designs that are used to study the relationship between antibiotic use and the emergence and spread of resistance, as well as highlight their main strengths and weaknesses.