Many physicians and patients hold the (unconscious) belief that intravenous antibiotic therapy is superior to oral therapy. This belief is also reflected in guidelines, where increasing severity of infection often leads to the recommendation of intravenous options only. But is this belief justified, and where does it come from? Treating with oral antibiotics has many potential advantages, such as fewer hospital admissions and the prevention of related complications. In this era of increasing demand for appropriate and efficient care, oral antibiotic treatment should replace intravenous treatment where possible. Here, we outline the crucial factors that should be considered when deciding between oral and intravenous treatment of infections: pharmacokinetics and dynamics, antibiotic resistance, and specific patient factors.