Success in clinical practice results from the combination of a clinician's experience, an understanding of patient preferences and factors that influence patient perceptions, and careful interpretation of data from clinical trials. However, successful clinical trials fulfil rigid methodological requirements in order to provide a basis from which to evaluate the place of a drug within a therapeutic strategy. Their translation into practice is therefore complicated by an intrinsic tension between the requirements for scientific methods that minimize error, and the need for clinically relevant data. In practice, the clinician has the flexibility to individualize epilepsy management to maximize benefits and minimize adverse effects of antiepileptic drug (AED) therapy. AED adverse effects and psychiatric comorbidity, in particular depression, have a profound impact on subjective health status; systematic screening for these confounding variables can guide clinical management and optimize quality of life. In addition, patient preferences can be acknowledged in any management plan. To achieve success in clinical practice, we need to remember that the information gleaned from clinical trials provides only part of the picture and needs to be augmented by our clinical experience, patient assessment (including routine screening for adverse effects and depression) and patient preference.