Until the last decade, studies of the timing of early symptom emergence in autism spectrum disorder (ASD) relied upon retrospective methods. Recent investigations, however, are raising significant questions about the accuracy and validity of such data. Questions about when and how behavioral signs of autism emerge may be better answered through prospective studies, in which infants are enrolled near birth and followed longitudinally until the age at which ASD can be confidently diagnosed or ruled out. This review summarizes the results of recent studies that utilized prospective methods to study infants at high risk of developing ASD due to family history. Collectively, prospective studies demonstrate that the onset of ASD involves declines in the rates of key social and communication behaviors during the first years of life for most children. This corpus of literature suggests that regressive onset patterns occur much more frequently than previously recognized and may be the rule rather than the exception.