Failure to Thrive (FTT) is a multifactorial illness requiring the systematic application of evidence in conjunction with a multidisciplinary team-based approach. Evidence suggests most cases of FTT can be diagnosed using key elements of the patient history and physical examination including appropriate growth assessment, and that laboratory testing is usually unhelpful in determining an etiology. Despite this, there is wide variation in the definition, evaluation, treatment, costs, and outcomes of FTT patients, with subsequent burdens on the healthcare system. A suggested approach to the differential diagnosis and management of FTT is to review calories – inadequate caloric intake, excessive calorie losses, and/or increased caloric intake (i.e. increased metabolic demand) – while acknowledging the available resources along the continuum of patient care. Implementing evidence-based practice for FTT provides improvement opportunities for providers and potentially has significant impact on the healthcare system.