Purpose: The modified barium swallow study (MBSS) is a widely used videofluoroscopic evaluation of the functional anatomy and physiology of swallowing that permits visualization of bolus flow throughout the upper aerodigestive tract in real time. The information gained from the examination is critical for identifying and distinguishing the type and severity of swallowing impairment, determining the safety of oral intake, testing the effect of evidence-based frontline interventions, and formulating oral intake recommendations and treatment planning. The goal of this review article is to provide the state of the science and best practices related to MBSS. Method: State of the science and best practices for MBSS are reviewed from the perspectives of speech-language pathologists (SLPs) and radiologists who clinically practice and conduct research in this area. Current quandaries and emerging clinical and research trends are also considered. Results: This document provides an overview of the MBSS and standards for conducting, interpreting, and reporting the exam; the SLPs’ and radiologist’s perspectives on standardization of the exam; radiation exposure; technical parameters for recording and reviewing the exam; the importance of an interdisciplinary approach with engaged radiologists and SLPs; and special considerations for examinations in children. Conclusions: The MBSS is the primary swallowing examination that permits visualization of bolus flow and swallowing movement throughout the upper aerodigestive tract in real time. The clinical validity of the study has been established when conducted using reproducible and validated protocols and metrics applied according to best practices to provide accurate and reliable information necessary to direct treatment planning and limit radiation exposure. Standards and quandaries discussed in this review article, as well as references, provide a basis for understanding the current best practices for MBSS.