Even though at least 10% (if not 20%) of those who experience a first lifetime episode of depression will subsequently develop bipolar disorder, the alliance of academic and industry research agendas that leads to developing and testing new antidepressants has failed to produce a sufficient knowledge base. It is therefore impossible to apply a truly empirical approach to guide the treatment of people with bipolar depression. Consequently, there are holes in contemporary evidenced-based practice guidelines large enough to drive a truck through; furthermore, there are some recommendations that have no factual basis other than expert opinion. However, with new research emerging on lamotrigine and olanzapine, in addition to the pending results of larger studies supported by the National Institute of Mental Health and the Stanley Foundation, there is evidence that some progress is being made.