Background Although the presence of wide-ranging neuropsychological deficits in individuals with major depression is well established, few studies have investigated the nature of cognitive impairment in patients with bipolar disorder. Aims To review research of the neuropsychology of bipolar disorder, with special attention to the relationship between mood and cognitive functioning. Method Literature review. Results Findings generally demonstrate mania-related impairments on conventional neuropsychological tests, with direct comparisons of patients with mania and patients with depression failing to find group differences. More recent work has sought to differentiate these disorders by employing tasks with affective components. This research has demonstrated biases for processing positive and negative stimuli in patients with mania and depression, respectively. Conclusions Future studies, employing tasks that require cognitive and emotional processing, should improve our understanding of the deficits observed in depression and mania. Neuroimaging studies of the neural regions that underlie cognitive processing of affective meaning suggest that the medial and orbitofrontal prefrontal cortex may be particularly involved.