Background: The inappropriate, irrational use or misuse of antibiotics is observed in all health systems and in all patients’ groups worldwide, especially for children, where antibiotics continue to be the drugs most commonly prescribed. Methods: A cross-sectional study was conducted in all public pediatric clinics in the Republic of Cyprus, from April to May 2015. A questionnaire was distributed to pediatricians in order to identify the antibiotic prescription practices in common childhood diseases and attitudes towards Pharmacovigilance. The SPSS 19.0 was used for the statistical analysis. In total 42 pediatricians and pediatric residents filled out the questionnaire. Results: A significant percentage of the respondents administered empirical therapy for possible group A streptococcus infection (59.5%), they implemented the “watchful waiting” tactic in acute otitis media (66.7%), whereas 11.9% of them administered antibiotics for the prevention of secondary respiratory tract infections. The majority of physicians did not feel diagnostic uncertainty leading to antibiotics prescribing (90.2%) and their prescribing habits were not influenced by parental demand (80.5%). Although 23.1% of physicians observed often/very often Adverse Drug Reactions (ADRs) after antibiotic administration during their clinical practice, however, 47.6% of the pediatricians declared that they did not report them. Conclusion: Health professionals’ continuing education on the use of therapeutic guidelines and protocols and the development of Pharmacovigilance programs could significantly contribute to the avoidance of the misuse of antibiotics in hospital care as well as to health professionals’ awareness on rational prescribing.