This paper reports on a prospective, longitudinal study of children prenatally exposed to poly-substances, who were reared under minimal postnatal risk conditions. The aim of the study was to examine whether the substance-exposed group exhibited a higher level of attention-related problems than a group of age-matched, nonexposed children. The substance-exposed children (n = 42) evinced significant elevated levels of impulsivity and attention problems on the CBCL and on the ADHD rating scale at ages 2 and 4 1/2 as compared to the non-exposed peers (n = 50). The severity of the attention problems in the substance-exposed group was related to dysfunction in the area of perceptual performance and motor abilities assessed on the McCarthy scales. This finding lends support to the hypothesis of a neurological basis of the behavioral problems. The combination of attention problems and specific cognitive deficits indicates that the children exposed to poly-substances in utero had symptoms associated with ADHD/DAMP. The study suggests that even if children experience adequate care after birth, the accumulation of risk factors associated with prenatal substance exposure is still a potential contributor to impulsivity and attention-related problems in preschool children.