Research in developmental psychopathology and clinical staging models has increasingly sought to identify trans-diagnostic biomarkers or neurocognitive deficits that may play a role in the onset and trajectory of mental disorders and could represent modifiable treatment targets. Less attention has been directed at the potential role of cognitive-emotional regulation processes such as ruminative response style. Maladaptive rumination (toxic brooding) is a known mediator of the association between gender and internalizing disorders in adolescents and is increased in individuals with a history of early adversity. Furthermore, rumination shows moderate levels of genetic heritability and is linked to abnormalities in neural networks associated with emotional regulation and executive functioning. This review explores the potential role of rumination in exacerbating the symptoms of alcohol and substance misuse, and bipolar and psychotic disorders during the peak age range for illness onset. Evidence shows that rumination not only amplifies levels of distress and suicidal ideation, but also extends physiological responses to stress, which may partly explain the high prevalence of physical and mental co-morbidity in youth presenting to mental health services. In summary, the normative developmental trajectory of rumination and its role in the evolution of mental disorders and physical illness demonstrates that rumination presents a detectable, modifiable trans-diagnostic risk factor in youth.