<p>Serious mental illnesses (SMIs), including major depressive disorder, bipolar disorder, and schizophrenia, have long been linked to cognitive decline, multiple chronic medical conditions, and premature mortality. These factors significantly contribute to the severe disability seen in SMIs, extending beyond the severity of psychopathology and indicating a premature aging phenotype associated with these conditions. The mechanisms that underlie the relationship between SMIs and the premature aging phenotype are not well understood, but recent evidence suggests that individuals with SMIs may exhibit accelerated biological aging. In this review, we present a comprehensive analysis of the current literature, demonstrating the potential association of SMIs (focusing on mood disorders and schizophrenia spectrum disorders) with abnormalities across various hallmarks of biological aging. We further evaluate how these abnormalities result in more severe psychopathology, poorer treatment outcomes, and a premature aging phenotype in SMIs. We also explore how the hallmarks of biological aging can be affected by behavioral and lifestyle factors, their interconnectedness, and whether they can be considered novel treatment targets for SMIs. In summary, we present robust evidence that accelerated biological aging is a significant biological characteristic of SMIs, contributing to the multiple adverse outcomes observed in these conditions.</p>