Diabetic patients are at increased risk of complicated skin, skin structure and bone infections including infections of diabetic foot ulcerations (DFU). Analyses of epidemiology and microbial pathogenicity show that staphylococci seem to be predestined to induce such infections. In addition, multidrug resistance particularly due to an increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) seems to be the challenge for effective antibiotic therapy. With regard to infections with MRSA, classical agents like vancomycin, linezolid, fosfomycin or trimethroprim–sulphametoxazol might be agents of choice in DFU. New-generation drugs including broad-spectrum tetracyclines like tigecycline, first and second generation of cyclic lipopeptides, anti-MRSA β-lactams including ceftobiprole and anti-MRSA antibodies are developed or in progress and the hope for the future.