With the emerging interest in documenting and understanding muscle atrophy and function in critically ill patients and survivors, ultrasonography has transformational potential for measurement of muscle quantity and quality. We discuss the importance of quantifying skeletal muscle in the intensive care unit setting. We also identify the merits and limitations of various modalities that are capable of accurately and precisely measuring muscularity. Ultrasound is emerging as a potentially powerful tool for skeletal muscle quantification; however, there are key challenges that need to be addressed in future work to ensure useful interpretation and comparability of results across diverse observational and interventional studies. Ultrasound presents several methodological challenges, and ultimately muscle quantification combined with metabolic, nutritional, and functional markers will allow optimal patient assessment and prognosis. Moving forward, we recommend that publications include greater detail on landmarking, repeated measures, identification of muscle that was not assessable, and reproducible protocols to more effectively compare results across different studies.