Offspring of parents with bipolar disorder (O-BP) is a high-risk cohort for mental illness in general and bipolar disorder (BD) specifically. This review aims to delineate the main clinical features of O-BP, including the psychopathology, interpersonal functioning, temperamental and personality features, neurocognitive deficits and neurobiological dysfunctions. Evidence indicates that several internalizing and externalizing symptoms/disorders are more prevalent in O-BP than in offspring of healthy control parents (O-HC). Furthermore, O-BP exhibits poorer interpersonal functioning than O-HC. Moreover, O-BP also endorses higher activity level, emotionality and behavioral disinhibition compared to O-HC. Besides, O-BP displays greater deficits on memory, cognitive flexibility and social cognition compared to O-HC. Finally, O-BP exhibits dysfunctional modulation in cortico- subcortical areas, more white matter abnormalities and higher cortisol basal levels compared to O-HC. Overall, these findings are discussed regarding the natural course and potential risk factors or endophenotypes for major mood disorders in general and BD specifically.