Over the past 10 years, theorists have suggested that bipolar disorder symptoms result from increases and decreases in the activity of the Behavioral Activation or Facilitation System (BAS or BFS) and the Behavioral Inhibition System (BIS). These neurobehavioral systems are thought to determine the intensity of affective and behavioral responses to incentives and threats. This study examined cross-sectional and prospective associations of self-reported BIS and BAS with mania and depression in a sample of 59 individuals diagnosed with Bipolar I disorder. Depression was tied to BIS, pointing to the importance of sensitivity to threats in depression. However, links between BIS and depression appeared state-dependent. BAS subscales did not correlate with manic symptoms in a state-dependent manner; however, BAS (total scale and reward responsiveness subscale) predicted relative intensification of manic symptoms over time. Thus, evidence suggests that BAS sensitivity may constitute a vulnerability to mania among persons diagnosed with bipolar disorder. Discussion focuses on the integrative potential of the BIS/BAS constructs for linking psychosocial and biological research on bipolar disorder.