Multiple advances have been made in our understanding of pathobiology of chronic 
lymphocytic leukemia (CLL). These developments in the laboratory include new 
prognostic markers, risk stratification of the disease and newer therapeutic 
agents in CLL. These advances in CLL have come a long way in the past three 
decades since the development of Rai and Binet clinical staging systems. 
Important strides in the pathobiology, from defining mutational status of IGHV, 
to B-cell receptor (BCR) signaling pathways and CLL microenvironment have made a 
major difference in our understanding of this disease. Mutational status of 
immunoglobulin heavy chain genes (IGHV), CD38 and Zap-70, chromosomal 
aberrations and newer mutations, are the most clinically relevant prognostic 
markers. Chemoimmunotherapy (CIT) has become the treatment of choice for young 
and fit CLL patients. Various inhibitors of BCR signaling pathways and 
immunomodulatory drugs have shown efficacy in clinical trials. The most recent 
advance is the use of chimeric antigen receptor therapy (CAR) based on 
autologous T-lymphocytes. Nevertheless, CLL remains an incurable disease today. 
Coordinated developments between laboratory and clinic will hopefully translate 
into a cure for CLL. This short review focuses on advances in prognostication 
and therapy in CLL.