Self-medication, usually with over-the-counter (OTC) medication, is reported as a community health problem that affects many people worldwide. Most self-medication practice usually begins with the onset of adolescence. A school-based cross-sectional study was conducted in Mafraq Governorate, Jordan, using a simple random sampling method to select 6 public schools from a total of 34 schools. The total sample consisted of 422 school students from Grades 7 through 12. Measures of central tendency and ?[superscript 2] were used to compare the difference between the categorical variables. The prevalence of self-medication among the participants was 87.0%. Nearly 75% of self-medication was used for pain relief. The prevalence of self-medication among school students is very high and increases with age. School nurses and other local health-care workers must coordinate with school principals to disseminate health education campaigns about safe use of medication to provide awareness and education to school students, parents, and families.