Background: Bipolar disorder (short: BD) is a severe illness with very heterogeneous trajectories. While some of the patients show no or hardly any long-term impairments, other affected individuals show substantial neurocognitive deficits with a clear decline in psychosocial functioning. Which factors influence the course of the disease is the subject of current research efforts. Objective: This review presents the long-term course of bipolar disease and the factors influencing it. In particular, differential trajectory types are discussed. The cognitive and psychosocial functional level as well as the psychopathological characteristics of the disease are elucidated. In addition, biological factors and treatment approaches influencing the course and prognosis are identified. Material and methods: Literature search using PubMed focusing on longitudinal studies over several years (see online supplement). Results: To date, there are only a few predictors and biomarkers that allow prediction of long-term progression. None have been sufficiently studied to enable clinical use. Appropriate pharmacological and psychotherapeutic treatment of those affected is essential to avoid renewed episodes of the disease. Discussion: The long-term course of bipolar disorder is highly heterogeneous and multifaceted. Despite intensive research efforts, no predictors have yet been identified that reliably predict the clinical course. This makes further research all the more important in order to offer individualized therapy options, develop new therapies and positively influence the course of the disease at an early stage.