Objectives: Recent reviews lack important information on the high cost-of-illness worldwide for bipolar disorder (BD). Therefore, the present study systematically analyzed those costs, their driving components, and the methodological quality with which the few existing cost-of-illness investigations have been performed. Methods: In June 2012, we conducted a systematic literature review of electronic databases to identify relevant cost-of-illness studies published since 2000. Their methodological quality was assessed. Costs were standardized by first extrapolating them to 2009 using country-specific gross domestic product inflators and then converting them into US dollars via purchasing power parities (PPP). Results: The main characteristics of 22 studies were evaluated. Ignoring outliers, costs per capita ranged from 8,000 to 14,000 US$-PPP for overall direct healthcare, from 4,000 to 5,000 US$-PPP for direct mental healthcare, and from 2,500 to 5,000 US$-PPP for direct BD-related care. Indirect costs ranged from 2,000 to 11,000 US$-PPP. Inpatient care was the main cost driver in three studies; drug costs, in two studies. Methodological quality was deemed satisfactory. Conclusions: The cost variance was great between studies. This was likely due to differences in methodology rather than healthcare systems, thereby making such comparisons difficult. The results showed that BD has a substantial economic burden on society. To gain more evidence, international standardized checklists are needed when undertaking cost-of-illness studies.