Recent work has suggested an association between the orbitofrontal cortex in humans and practical decision making. The aim of this study was to investigate the profile of cognitive deficits, with particular emphasis on decision-making processes, following damage to different sectors of the human prefrontal cortex. Patients with discrete orbitofrontal (OBF) lesions, dorsolateral (DL) lesions, dorsomedial (DM) lesions and large frontal lesions (Large) were compared with matched controls on three different decision-making tasks: the Iowa Gambling Task and two recently developed tasks that attempt to fractionate some of the cognitive components of the Iowa task. A comprehensive battery including the assessment of recognition memory, working memory, planning ability and attentional set-shifting was also administered. Whilst combined frontal patients were impaired on several of the tasks employed, distinct profiles emerged for each patient group. In contrast to previous data, patients with focal OBF lesions performed at control levels on the three decision-making tasks (and the executive tasks), but showed some evidence of prolonged deliberation. DL patients showed pronounced impairment on working memory, planning, attentional shifting and the Iowa Gambling Task. DM patients were impaired at the Iowa Gambling Task and also at planning. The Large group displayed diffuse impairment, but were the only group to exhibit risky decision making. Methodological differences from previous studies of OBF patient groups are discussed, with particular attention to lesion laterality, lesion size and psychiatric presentation. Ventral and dorsal aspects of prefrontal cortex must interact in the maintenance of rational and 'non-risky' decision making.