The article considers the arguments that can provide a rationale for treatment policy in patients with epilepsy after failure of monotherapy with a first antiepileptic drug (AED). When choosing alternative monotherapy or early polytherapy with AEDs, one should consider a diversity of criteria: the mechanism of action, pharmacokinetic and pharmacodynamic properties, efficacy, and safety profile of AEDs, disease features, individual patient characteristics, and social factors. The choice of the right AED treatment policy in the early stages of the disease is important for patients because the inadequate control of seizures can result in irreversible psychosocial consequences and reduce the chance to eliminate future disabling seizures.