In this chapter, we will focus on childhood maltreatment and its role in the vulnerability to BD.We will review how childhood maltreatment and trauma not only predispose to the development of BD but also to a more unstable, pernicious, and severe clinical expression of the disorder. This environmental risk factor is suggested to be part of a multiple hit model of vulnerability, involving not only early stressors (prenatal and postnatal ones) but also interactions with the genetic background of individuals and with other stressors occurring later in life. We will also review how childhood maltreatment and trauma may modify the brain functioning and circuits and alter some biological pathways in BD, hence leading to psychopathology. Finally, we will briefly discuss the implications for clinical practice and treatment.