This review provides clinicians with a comprehensive overview of indirect calorimetry including the principles, methodology, technologic advancements, benefits, and challenges. Clinical applications for indirect calorimetry and the potential limitations are specifically addressed for both the inpatient and outpatient setting. Measurement of energy expenditure is the most accurate method to assess energy needs. Indirect calorimetry remains a gold standard in measuring energy expenditure in the clinical settings. The benefits of providing optimal nutrition for recovery from illness and chronic health management are well documented. Indirect calorimetry offers a scientifically-based approach to customize a patient's energy needs and nutrient delivery to maximize the benefits of nutrition therapy. With recent advances in technology, indirect calorimeters are easier to operate, more portable, and affordable. Increased utilization of indirect calorimetry would facilitate individualized patient care and should lead to improved treatment outcomes.