Purpose: Lower urinary tract symptoms are common in the United States population, leading to significant economic, quality of life and public health issues. The burden will increase as the population ages, and risk factors for lower urinary tract symptoms, including diabetes and obesity, remain highly prevalent. Improving clinical management and establishing the knowledge base to prevent lower urinary tract symptoms will require a comprehensive research approach that examines factors beyond the lower urinary tract. While the study of extra-lower urinary tract factors has increased recently, current urological research does not systematically account for the broad set of potential contributing factors spanning biological, behavioral, psychological/executive function and sociocultural factors. A comprehensive assessment of potential contributors to risk, treatment response and progression is necessary to reduce the burden of this condition in the United States. Materials and Methods: We considered challenges to continuing the predominantly lower urinary tract dysfunction centric approach that has dominated previous research of lower urinary tract symptoms. Results: We developed a new, comprehensive framework for urology research that includes a broader set of potential factors contributing to lower urinary tract symptoms. This framework aims to broaden research to consider a comprehensive set of potential contributing factors and to engage a broad range of researchers in the investigation of as many extra-lower urinary tract factors as possible, with the goal of improving clinical care and prevention. Conclusions: We propose a new framework for future urology research, which should help to reduce the medical and economic burden of lower urinary tract symptoms in the United States population.