Whilst it is established that the optimal treatment for chronic lymphocytic leukaemia (CLL) patients is frontline FCR chemoimmunotherapy, this disease is commonly seen in older patients who are often not fit enough for this dug combination. The standard alternative to FCR is chlorambucil; however recent research has shown promising results for alternatives such as bendamustine. Prof Peter Hillmen outlines how clinicians should decide upon the correct alternative to FCR, outlines the role of minimal residual disease (MRD) eradication in CLL treatment and explains how a greater understanding of the B-cell receptor pathway is helping researchers advance the treatment of CLL.