The basic concepts of positron emission tomography (PET) and single photon emission computed tomography ( SPECT) scanning are introduced, and the two modalities are compared. Applications to bipolar disorder ( BD) are reviewed. Regional cerebral metabolic rate and blood flow, often used as surrogate measures of neuronal synaptic activity, are increased in the frontal lobes in both unipolar and bipolar depression. In mania, metabolism increases in the dorsal cingulate cortex, striatal regions, and the nucleus accumbens, as well as in limbic structures of the temporal lobes, but decreases in dorsolateral prefrontal cortex, possibly reflecting its loss of modulatory control over limbic structures. Specifically targeted PET radioligands are used to investigate neurotransmitter systems. D1 receptor binding potentials are reduced in frontal cortex, but striatal D2 receptor density is normal in all phases of non-psychotic BD. Psychotic BD patients show higher D2 receptor densities in the caudate, which correlate with the degree of psychosis but not mood symptoms. The serotonin transporter shows increased density in the thalamus, dorsal cingulate cortex, medial preftontal cortex, and insula of depressed BD patients. In the dorsal cingulate cortex and insula, it correlates with anxiety (and in the cingulate, with suicide attempts).