Skin infections represent an important public health issue and cost-driver. Additionally, chronic skin lesions are sometimes colonized by Gram-negative species. Topical therapies are a key component in the management of mild-to-moderate skin infections. In such cases, topical antibiotics may be preferable to systemic treatment, since they maximize the effective doses at the site of infection while minimizing the systemic side effects of the drugs. However, the prevalence of resistant strains is steadily increasing and cases of sensitization are not uncommon. As a consequence, the ideal topical antibiotic should be selective (thus, minimizing cross-resistance), have weak sensitization potential, penetrate the skin efficiently, reach adequate local doses at the site of infection, and finally be available in different formulations matching patients' preferences and needs. Fusidic acid (FA) is a selective antibiotic available in several topical formulations. Pharmacokinetic and pharmacodynamic studies have shown that, contrary to other topical antibiotics such as gentamicin or mupirocin, FA reaches high antimicrobial concentration at deep skin layers after topical application either on intact or damaged epidermis. Several randomized controlled trials demonstrated that FA, in its various topical formulations, is very effective in treating skin infections, given its high bactericidal activity against S. aureus (including strains resistant to penicillin, methicillin, ampicillin, cloxacillin), S. epidermidis, Streptococcus pyogenes, Propionibacterium acnes, Corinebatteria, Clostridia. Additionally, FA presents a low risk of resistance even in methicillin-resistant S. aureus strains, a common pathogen implied in the etiology of skin infections and infected atopic eczema. Such feature makes FA particularly useful in the management of these medical conditions. Finally, possibly due to its large steric effect, FA has proved a very low risk of contact sensitization. Overall, data on FA efficacy, safety, sensitization potential, resistance profile and spectrum selectivity make it a first-choice option in the treatment of primary and secondary skin infection.