HLA-G appears to be involved in regulatory functions counteracting the cellular immune response of T and NK cells by several pathways. We here summarize the HLA-G expression patterns in leukaemia with emphasis on the clinical relevance of this expression for disease progression. Especially in patients with B-chronic lymphocytic leukaemia (B-CLL) the HLA-G expression on B-CLL cells was strongly associated with a reduced treatment-free survival. The corresponding immunological parameters point to a broad immunosuppression in these patients. Thus, HLA-G seems to contribute to the impaired immune response in B-CLL supporting disease progression.