While antibiotic resistance has grabbed the headlines and the attention of the pharmaceutical industry, the lack of susceptibility of biofilms formed both on animate and inanimate surfaces deserve greater attention from the industry, medical practitioners and regulators. The current literature tells us that the inherent tolerance to antibiotics demonstrated by antibiotic-sensitive organisms when grown as a biofilm clearly identifies a major disconnect between our current practices in antimicrobial development, diagnostics and efficacy in patient treatment. A paradigm shift is required in the way we utilize conventional antimicrobials and in the way we screen for next-generation antibiotics with efficacy to treat biofilms associated with chronic, recurrent and device related infections. This paradigm shift must not only take place in industry but also in how drugs are brought to the marketplace for acceptance.