The present study examined the genetic and environmental etiology underlying the Big Five personality traits and perceived stress, concurrently and longitudinally. In study 1, we used the twin sample from the National Longitudinal Study of Adolescent to Adult Health (Add Health IV) data. The results indicated that about 70% of the association between the Big Five personality traits and perceived stress was due to genetic influences. In study 2, we used the twin sample from the Midlife in the United States Survey (MIDUS I and II) to examine the genetic and environmental influences underlying the longitudinal relations between the Big Five personality traits and perceived stress. The results suggested that continuity in perceived stress was primarily accounted for by genetic influences, and changes in perceived stress were mainly due to nonshared environmental influences. The continuity in the association between the five personality traits and perceived stress was largely accounted for by genetic factors, and nonshared environmental factors made greater contributions to changes in the association between personality traits and perceived stress. Among the Big Five personality traits, the genetic components in conscientiousness and neuroticism made substantial contributions to the genetic link between personality traits and perceived stress across both studies.