The present invention is directed to the combination therapy of an anti-CD20 antibody with a Bcl-2 inhibitor and a MDM2 inhibitor for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with a type I anti-CD20 antibody or an afucosylated humanized B-Ly1 antibody and a Bcl-2 inhibitor and a MDM2 inhibitor.