Objective: It is a widely held belief that bipolar disorder is progressive in nature; however, some recent reviews have questioned this belief. The objective of the present systematic literature review is to present updated evidence for the associations between the number of affective episodes and (1) the risk of recurrence of episodes, (2) the probability of recovery from episodes, (3) severity of episodes, (4) the threshold for developing episodes, and (5) progression of cognitive deficits in bipolar disorder. Methods: A systematic review comprising an extensive literature search conducted in Medline, Embase, and PsychInfo up to September 2023 and including cross-references from identified papers and reviews. Results: Most of the five areas are still superficially investigated and hampered by methodological challenges. Nevertheless, studies with the longest follow-up periods, using survival analysis methods and taking account of the individual heterogeneity, all support a clinical progressive course of illness. Overall, the increasing number of affective episodes seems to be associated with (1) an increasing risk of recurrence, (2) an increasing duration of episodes, (3) an increasing symptomatic severity of episodes, (4) a decreasing threshold for developing episodes, and (5) an increasing risk of developing dementia. Conclusion: Although the course of illness is heterogeneous, there is evidence for clinical progression on average for patients with bipolar disorder.