Most children and adolescents attending mental health services exhibit severe affective and behavioral dysregulation. The dysregulation profile (DP) seems to be an indicator of self-regulatory problems, overall psychopathology, symptom severity, and functional impairment. Although there are studies signaling its importance as a marker of severe psychopathology and long-term impairment, little is known about its predictors. We reviewed the existing literature and found biological and environmental factors associated with the DP. The DP seems to have high heritability rates, blunted hypothalamic-pituitary-adrenal axis responses at stress tasks, and attention problems regardless of emotional context. Some family factors (such as abnormal qualities of upbringing, lower effortful control, parental hostility, and parental substance use disorders) are also related to the DP. More research about specific predictors of the DP is clearly needed. Longitudinal studies would help identify them more clearly.