Mood disorders represent a significant global health concern, with both major depressive disorder (MDD) and bipolar disorder (BD) contributing to a substantial burden of disability. A significant challenge in the field of psychiatry is the distinction between unipolar depression and bipolar depression. It is not uncommon for individuals initially diagnosed with MDD to subsequently convert to BD. This chapter examines the diagnostic conversion from MDD to BD, with a focus on the neurobiological, clinical, and genetic factors that influence this transition. A misdiagnosis may result in the administration of an inappropriate treatment plan. This chapter identifies predictive markers, including early-onset depression, mood instability, and family history of BD, which can assist in identifying individuals at risk for conversion. Emerging tools, such as neuroimaging and biological profiling, offer promising avenues for improving diagnostic accuracy. In addition, the chapter addresses treatment strategies aimed at preventing diagnostic conversion, with a focus on early interventions for high-risk populations. By advancing diagnostic and therapeutic approaches, the ultimate goal of researchers is to improve outcomes for individuals vulnerable to developing BD and provide a better understanding of the bipolar trajectory.