Although the incidence of acute mastoiditis has been substantially reduced since the introduction of antibiotic therapy, mastoiditis complications are still commonly seen in the pediatric population. Many of these cases require lengthy hospitalizations and extensive medical and surgical interventions. Accordingly, a safe, effective, and resourceful diagnostic and therapeutic plan must be executed for the workup and treatment of each patient suspected of having acute mastoiditis. With thorough clinical evaluations, early diagnosis, and close follow-up, a large proportion of children with severe acute otitis media or early stage mastoiditis can be managed in the primary care setting without immediate surgical specialty involvement. This review presents an overview of the anatomical and pathophysiological considerations in acute mastoiditis and offers pediatricians a practical, evidence-based algorithm for the diagnostic and therapeutic approach to this disease.