Crowding in the mixed dentition is usually the main reason for parents bringing their children to visit pediatric dental clinic. In cases of severe crowing that requires extraction, serial extraction starting from the mixed dentition stage is a valid method of treatment. Therefore, this article aims to review and discuss issues in the indications of serial extraction, the sequence of serial extraction, the effect of serial extraction, the spontaneous changes in the dentition after serial extraction, the importance of active orthodontic therapy after serial extraction, the comparison between serial extraction and late extraction of premolars, as well as the stability and relapse. Thus, under appropriate considerations of serial extraction, the choice of treatment can be preferable for each patient.