A recently published pharmacokinetic trial showed that the fluoroquinolone moxifloxacin administered to healthy volunteers at the single oral dose of 400mg accumulates in prostatic secretions (PS) up to a median concentration of 3.99 mg/L and reaches a PS/plasma concentration ratio of 1.57, far higher than values shown by other fluoroquinolones such as norfloxacin (ratio 0.1) or ciprofloxacin (ratio 0.2). Ion trapping mechanisms were hypothesised to be among the determinants of this effect. However, whether ion trapping would solely account for the observed differences in fluoroquinolone pharmacokinetics was left to further research and discussion. In this hypothesis paper, we review various published evidence on the tissue distribution of moxifloxacin and other quinolones, suggesting that increased lipophilicity, binding to cellular matrices and fast cellular uptake/release kinetics may be mechanisms compatible with enhanced prostatic accumulation and secretion of fourth-generation fluoroquinolones.