The most severe consequence of iron depletion is iron deficiency anemia (IDA), and it is still considered the most common nutrition deficiency worldwide. Although the etiology of IDA is multifaceted, it generally results when the iron demands by the body are not met by iron absorption, regardless of the reason. Individuals with IDA have inadequate intake, impaired absorption or transport, physiologic losses associated with chronological or reproductive age, or chronic blood loss secondary to disease. In adults, IDA can result in a wide variety of adverse outcomes including diminished work or exercise capacity, impaired thermoregulation, immune dysfunction, GI disturbances, and neurocognitive impairment. In addition, IDA concomitant with chronic kidney disease or congestive heart failure can worsen the outcome of both conditions. In this review, the prevalence of IDA related to confounding medical conditions will be described along with its diverse etiologies. Distinguishing IDA from anemia of chronic disease using hematologic measures is reviewed as well. In addition, current diagnostic strategies that are inclusive of clinical presentation, biochemical tests, and differential diagnosis will be outlined, followed by a discussion of treatment modalities and future research recommendations.