Rituximab (anti-CD20 antibody) has been approved as a treatment for B-cell associated hematological disorders. CD20 expression and its complement regulatory proteins and membrane binding structures play a crucial role in rituximab efficacy. Complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity are the major mechanisms by which rituximab eliminates B cells. The efficacy of anti-CD20 varies in different diseases. Rituximab was approved as a successful treatment in diseases such as non-Hodgkin lymphomas, particularly diffuse large B-cell lymphoma and follicular lymphoma. In addition, rituximab has recently shown promising results with several autoimmune diseases; it was approved for rheumatoid arthritis as well as being used for other diseases such as systemic lupus erythematosus. Likewise, rituximab was successfully used for incompatible ABO organ transplantation instead of the invasive splenectomy procedure. This review will discuss the use of rituximab for different hematological diseases.