A number of new treatment options have recently emerged for chronic lymphocytic 
leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor 
ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor 
idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new 
anti-CD20 antibodies obinutuzumab and ofatumumab. Most of these agents are 
already included into treatment algorithms defined by international practice 
guidelines, but more clinical investigations are needed to answer still 
remaining questions. Ibrutinib was proven as a primary choice for patients with 
the TP53 gene deletion/mutation, who otherwise have no active treatment 
available. Idelalisib with rituximab is also an active therapy, but due to 
increased risk of serious infections, its use in first-line treatment is limited 
to patients for whom ibrutinib is not an option. A new indication for ibrutinib 
was recently approved for older patients with comorbidities, as an alternative 
to the already existing indication for chlorambucil with obinutuzumab. The use 
of kinase inhibitors is already well established in recurrent/refractory 
disease. Immunochemotherapy with fludarabine, cyclophosphamide, rituximab (FCR) 
remains a major first-line option for many CLL patients without the TP53 gene 
deletion/mutation, and who have no significant comorbidities or history of 
infections, and is particularly effective in patients with favorable features 
including mutated IGHV status. There are a number of issues regarding novel 
therapies for CLL that need further investigation such as optimum duration of 
treatment with kinase inhibitors, appropriate sequencing of novel agents, 
mechanisms of resistance to inhibitors and response to class switching after 
treatment failure, along with the potential role of combinations of targeted 
agents.