Dermatologists often come across cases of skin and soft-tissue infections (SSTIs) which have diverse clinical presentations. Various local, systemic, and environmental risk factors predispose an individual to develop SSTIs. Topical antimicrobial agents are frequently used in superficial uncomplicated SSTIs, whereas systemic therapy is generally reserved for use in severe cases. However, emergence of resistance to these agents is becoming a common problem in clinical practice. This necessitates the use of other classes of antimicrobials for the effective treatment of SSTIs. Nadifloxacin, a potential drug belonging to the fluoroquinolone group, has various advantages such as binding to bacterial DNA gyrase and topoisomerase IV enzymes, inhibition of nor-A efflux pump, survival in acidic pH, anti-MRSA activity, and biofilms penetration. It has also shown least development of resistance since its introduction. Although its topical formulation has shown superior efficacy as an anti-acne agent, there are no specific guidelines for its appropriate use in SSTIs. Hence, a panel of experts was formed, under whose guidance an extensive literature search was performed in MEDLINE, Cochrane Library, and Science Direct databases. Using the modified Delphi technique, the available evidence was reviewed and corresponding recommendations were given for the use of topical Nadifloxacin as an empirical treatment in SSTIs.