First-onset tics during stimulant treatment of attention-deficit-hyperactivity disorder (ADHD) are clinically relevant and remain a matter of scientific debate. Because there are limited clinical trials analyzing the risk of first-onset tics in stimulant-treated ADHD, a comprehensive evaluation is required for evidence-based clinical recommendations. An analysis of studies with high methodological quality (i.e. double-blind placebo-controlled) on first-onset tics during stimulant treatment of ADHD revealed that there seems to be no elevated risk of first-onset tics in children undergoing this treatment. Although a close temporal relationship might be seen in a few patients, the role of treatment duration, dose of stimulant, genetic vulnerability, and developmental aspects need to be further explored to clarify possible pathophysiological mechanisms of tic emergence under stimulant treatment. The results of high quality studies, in addition to specialized studies with methodological limitations, suggest that stimulants are the criterion standard for the safe and successful treatment of ADHD.