Anemia is a very common complication of chronic kidney disease (CKD). Anemia confers significant risk of cardiovascular disease and contributes to decreased quality of life. Anemia in CKD patients can be multi-factorial, including but not invariably due to the underlying renal insufficiency. Identifying the type of anemia is important in this group of patients and can often be challenging. Diagnosing anemia of renal disease due to erythropoietin (EPO) deficiency is a diagnosis of exclusion. Erythropoiesis stimulating agents (ESA) are the mainstay for the treatment of anemia secondary to CKD. However, over the last four years the use of ESA in the treatment of anemia in CKD patients has undergone a severe interrogation as several trials have reported adverse outcomes with targeting higher hemoglobin (Hb) levels with these agents. Thereby, this review describes the pathophysiology of anemia in CKD patients, diagnosis and the current role of ESA's as it relates to anemia of CKD as well as safety and efficacy of ESA's.