The mortality and morbidity due to suicidal behavior associated with bipolar disorder is the greatest among psychiatric diagnoses. To address this problem, it is essential to find predictors of future risk as well as protective factors. Studies from several international teams have demonstrated that for bipolar disorder, the presence of a depressive episode is the most robust predictor and risk increases as does depression severity. Protective factors such as older age and religious affiliation are also key moderators. The role of pharmacotherapy in suicidal behavior has been studied mostly utilizing data that are either observational and naturalistic, rather than experimental. Only one randomized, double-blind clinical trial has been conducted to date, although another one is underway. The comparison of lithium and valproate in terms of effect on suicidal behavior revealed no differences. Although the trial was not powered to detect small effect sizes, results suggest that the Relative Risk ratio generated from meta-analytic studies (RR∼ 5) is too optimistic. The trial also suggested that younger individuals may respond differently to pharmacotherapy, suggesting opportunities to personalize treatment approaches. Robust pharmacotherapy targeting both mood stabilization and depressive symptoms is essential and may assist in the quest against suicidal behavior.