Management of common infections and optimal use of antimicrobial agents are presented, highlighting new evidence from the medical literature that enlightens practice. Primary therapy of staphylococcal skin abscesses is drainage. Patients who have a large abscess (>5 cm), cellulitis or mixed abscess–cellulitis likely would benefit from additional antibiotic therapy. When choosing an antibiotic for outpatient management, the patient, pathogen and in vitro drug susceptibility as well as tolerability, bioavailability and safety characteristics of antibiotics should be considered. Management of recurrent staphylococcal skin and soft tissue infections is vexing. Focus is best placed on reducing density of the organism on the patient's skin and in the environment, and optimizing a healthy skin barrier. With attention to adherence and optimal dosing, acute uncomplicated osteomyelitis can be managed with early transition from parenteral to oral therapy and with a 3–4 week total course of therapy. Doxycycline should be prescribed when indicated for a child of any age. Its use is not associated with dental staining. Azithromycin should be prescribed for infants when indicated, whilst being alert to an associated ≥2-fold excess risk of pyloric stenosis with use under 6 weeks of age. Beyond the neonatal period, acyclovir is more safely dosed by body surface area (not to exceed 500 mg/m²/dose) than by weight. In addition to the concern of antimicrobial resistance, unnecessary use of antibiotics should be avoided because of potential later metabolic effects, thought to be due to perturbation of the host's microbiome.