Anemia is a commonly encountered problem in the clinical evaluation of children and adults. Broadly categorized, the causes of anemia relate to acute loss, inadequate production, or destruction of red blood cells. Review of readily available laboratory data, including the complete blood count, including red blood cell indices and the reticulocyte count, when combined with examination of the peripheral blood smear, leads to the creation of an appropriate differential diagnosis. This can then be further narrowed through targeted diagnostic testing. This approach can minimize the amount of additional laboratory investigation required and, when appropriate, lead rapidly to implementation of therapeutic intervention.