The concept of minimal residual disease (MRD) eradication in chronic lymphocytic leukaemia (CLL) is a relatively new one, as conventional therapy with alkylating agents is relatively ineffective and responding patients almost always have a significant tumour burden remaining at the end of treatment. However, a variety of novel therapies is now yielding higher response rates, and responses of better quality are now routinely achieved. This progress in therapy has been paralleled by an improvement in laboratory assays, allowing detection of CLL cells to levels as low as ten CLL cells in a million leukocytes. In this chapter we briefly review the existing methods for MRD assessment, the clinical relevance of MRD eradication in CLL, and the therapies available to attain this endpoint.