Although the empirical use of some antibacterial agents in various inflammatory diseases has proved beneficial in the past, it is only recently that the therapeutic anti-inflammatory potential of cyclines and macrolides has received attention worldwide. Other drugs like fosfomycin and some quinolones are also contenders for this role. Owing to the complexity of the inflammatory process, which involves many redundant cellular effectors and soluble mediators, and the obscure etiopathogenesis of many inflammatory diseases (some of which may be secondary to persistent infections), the precise mechanisms underlying the therapeutic benefit of anti-inflammatory antibiotics remain to be elucidated. Structure-activity relationships are the key to developing new anti-inflammatory agents derived from antibacterial drugs.