Background: The Stanley Foundation Bipolar Treatment Outcome Network (SFBN) recruited more than 900 outpatients from 1995 to 2002 from 4 sites in the United States (US) and 3 in the Netherlands and Germany (abbreviated as Europe). When funding was discontinued, the international group of investigators continued to work together as the Bipolar Collaborative Network (BCN), publishing so far 87 peer-reviewed manuscripts. On the 25th year anniversary of its founding, publication of a brief summary of some of the major findings appeared appropriate. Important insights into the course and treatment of adult outpatients with bipolar disorder were revealed and some methodological issues and lessons learned will be discussed. Results: The illness is recurrent and pernicious and difficult to bring to a long-term remission. Virtually all aspects of the illness were more prevalent in the US compared to Europe. This included vastly more patients with early onset illness and those with more psychosocial adversity in childhood; more genetic vulnerability; more anxiety and substance abuse comorbidity; more episodes and rapid cycling; and more treatment non-responsiveness. Conclusions: The findings provide a road map for a new round of much needed clinical treatment research studies. They also emphasize the need for the formation of a new network focusing on child and youth onset of mood disorders with a goal to achieve early precision diagnostics for intervention and prevention in attempting to make the course of bipolar illness more benign.