Biofilms associated with the human body, particularly in typically sterile locations, are difficult to diagnose and treat effectively because of their recalcitrance to conventional antibiotic therapy and host immune responses. The study of biofilms in medicine today requires a translational approach, with examination of clinically relevant biofilms in the context of specific anatomic sites, host tissues, and diseases, focusing on what can be done to mitigate their pathologic consequences. This review, which grew out of a discussion session on clinical biofilms at the 5th ASM Biofilm Conference in Cancun, Mexico, is designed to give an overview of biofilm-associated infections (BAI) and to propose a platform for further discussion that includes clinicians, medical microbiologists, and biofilm researchers who are stakeholders in advancing the scientific pursuit of better diagnosis and treatment of BAI to mitigate their human and healthcare costs. It also highlights the need for better diagnostic markers, which exploit the difference between planktonic and biofilm cells.