Substance abuse (SA) among children is a recognized challenge for policymakers and law enforcement and has life-threatening consequences owing to the impact on the children's development and the consequent increase in vulnerability. This work outlines several important issues related to SA among children: (1) SA prevalence including onset, common examples, extent, and spectrum of SA; (2) the presence of new psychoactive substances, which are rapidly spreading worldwide with limitations regarding their prevalence, detection, and interventions; (3) street children and their recruitment in drug supply; (4) SA and substance use disorder pathways, risk and protective factors for the development of SA; (5) SA consequences in the case of early initiation, including deaths; and (6) current preventive interventions for the pediatric population. In conclusion, this challenge requires consistent and unremitting attention in order to execute effective prevention programs with continuous re-evaluation of the situation.