There have been many studies that have examined various aspects of the pathophysiology of bipolar disorder, with many positive findings in several areas of neuroimaging and metabolic abnormality. These studies might allow some conclusions to be drawn about the underlying pathophysiology. Additionally, it is of significant interest to determine if there are pathophysiological differences between patients with bipolar disorder type I (BPD-I) and those with bipolar disorder type II (BPD-II). The present review examines imaging studies in bipolar patients of possible structural changes (magnetic resonance imaging (MRI)) functional changes (focusing on functional MRI (fMRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT)), and those examining brain chemistry (utilizing magnetic resonance spectroscopy (MRS)). Metabolic studies reviewed were those that examined 3-methoxy-4- hydroxyphenylglycol (MHPG), cellular calcium, and protein kinase C (PKC). The results clearly suggest that BPD patients differ from controls on many of these measures. However, while there is evidence from genetic studies suggesting possible differences between BPD-II patients and BPD-I patients, the neuroimaging and metabolic studies to date do not support this, and there appear to be no consistent pathophysiologica differences between these subtypes from evidence available at present.