The threshold chosen by categorical mental health classifications like DSM-IV-TR or ICD-10 for the diagnosis of bipolar disorders (BP) is too high, elevating the risk of misdiagnosing cases that closely resemble BP under several clinical variables like “major depressive disorder”. Acknowledging and providing the necessary weight to the BP subthreshold forms may improve the clinical practice and reduce the number of patients with misdiagnosis, creating opportunities for better treatment. Increasing evidence support the bipolar spectrum disorder (BPS) concept and factors such us earlier onset age of the first major depressive episode (MDE), brief duration of MDEs, rapid onset of MDEs, more than five previous MDEs, family history of BP, treatment-resistant depression, suicidal behavior, postpartum depression, atypical features, psychotic traits, irritability, overactivity, comorbidity with anxiety disorders, substance abuse, borderline personality disorder, migraine, and irritable temperament are well validated differentiators between unipolar and bipolar depressive disorders. Identifying those factors could increase the lifetime prevalence of BPS to at least 4.8%. New studies on the diagnosis and management of BP should focus on the development of diagnostics dimensional models with categorical benchmarks to recognize BP sub-threshold forms, on the selection of biomarkers for early identification of patients with BPS, especially those with BP family history, and on the promotion of joint efforts between academia, industry, government, and community to search new interventions in BPS management.