Despite effective pharmacotherapeutic and psychosocial strategies, approximately one third of adequately treated depressive patients do not reach remission and are considered treatment resistant. There are several factors associated with treatment-resistant depression (TRD). Underlying bipolarity is one of the important causes of TRD as it leads to a delayed diagnosis of bipolar disorder and inappropriate treatment. Assessment of bipolar features in every patient diagnosed with major depressive disorder (MDD), specifically in patients with TRD, is crucial. In the presence of bipolar features, interventions for TRD should be carried out carefully.