Long-term pharmacological treatment is the cornerstone of the management of bipolar disorder (BD). Clinicians typically select mood stabilizing medications from among several options through trial-and-error. This process could be optimized by using robust predictors of treatment response. We review clinical features and biological markers studied in relation to outcome of long-term treatment of BD. To date, the literature focused mostly on lithium and to a lesser extent on anticonvulsants valproate and lamotrigine. The most promising results show association of lithium response with certain clinical features (episodic clinical course and absence of rapid cycling, low rates of comorbid conditions, family history of bipolar disorder and lithium response) as well as low polygenic risk for schizophrenia and major depression. The clinical application of these findings remains limited, however, due to heterogeneity of the illness as well as unanswered questions about specificity of the effects of different medications.