Unlike most other drugs that only affect individual patients if used incorrectly for self-medication, misused antibiotics add to the global risk of increased spread of bacterial resistance. This review focuses on self-medication with antibiotics in Europe and its determinants. High prevalence of self-medication with antibiotics has been repeatedly found in Southern and Eastern European countries that also report high levels of antibiotic resistance. Despite being illegal, over the counter dispensation of systemic antibiotics occurs in several European Union Member States. A second major source of self-medication is the availability of “leftover” antibiotics which results from either patient non-compliance or dispensation of a larger number of tablets than needed for one single course. The potentially modifiable factors associated with self-medication are: availability of antibiotics without prescription, pack-based antibiotic dispensing system, misconceptions of the general public about the efficacy of antibiotics for minor illnesses and prescribing of antibiotics for minor ailments by physicians. Measures that may reduce and prevent self-medication include dispensation of exact tablet quantities in pharmacies as already implemented e.g. in the UK, Netherlands, the Czech Republic and the United States, and enforcement of existing laws prohibiting over-the-counter sales of antibiotics. Such measures should be embedded in a general policy to change the culture of antibiotic use by improving awareness of the general public and professionals about antibiotics and the risks associated with their use as well as reducing misconceptions about the need for antibiotics for minor ailments.