Anemia is defined as a decrease in the hemoglobin concentration below the age-and sex-matched lower limit (130 g/L in men and 120 g/L in women, WHO). When diagnosing anemia, a number of differential diagnoses must be considered. This is further complicated by the fact that anemias are often multicausal. A rational evaluation of anemia should therefore always take into account the epidemiological data and the individual patient's history. A central part of the diagnostic process is a classification, based on the size and the hemoglobin content of the red blood cells. For hypochromic microcytic anemia the most important cause worldwide is iron deficiency, with anemia of chronic disorders (ACD) and thalassemia the main differential diagnoses. For hyperchromic macrocytic anemia, the clinically most important causes are disorders of vitamin B12 and folic acid metabolism. Apart from those, most types of anemias fall within the normochromic normocytic group. In these cases, one should not try to investigate all possible causes by carrying out a fully comprehensive laboratory panel on the first blood sample. Instead, it is more appropriate to proceed step-by-step and to evaluate first the most frequent and clinically most important causes. This applies especially to geriatric and multimorbid patients where the diagnostic effort should be adjusted to the individual needs of the patient as well as their prognosis, both from an economical and from ethical point of view. In unexplained anemias, a hematological opinion should be considered because a bone marrow biopsy may be required to accurately evaluate the hematopoiesis and to exclude a hematological disorder.