Protein kinases (PKs) and lipid kinases (LKs) are good choices for targets of 
signal transduction therapy as these enzymes are involved in signaling pathways, 
and are often related to the pathogenesis of lymphoid malignancies. The 
attractiveness of PKs and LKs as drug able targets is enhanced by the fact that 
they are enzymes whose biological activity can be turned off by drugs that block 
their catalytic site. In the last few years small molecular kinase inhibitors 
(KIs) have been synthesized and become available for preclinical studies and 
clinical trials. The first KI, introduced into clinical practice in 1998, was 
imatinib mesylate, which became the first choice drug in chronic myeloid 
leukemia. More recently, several KIs have been developed to target the proximal 
B-cell receptor (BCR) signaling pathway including spleen tyrosine kinase 
inhibitor (Fostamatinib) and Bruton's tyrosine kinase inhibitors (Ibrutinib, 
AVL-263). These agents are currently evaluated in early clinical trials in 
chronic lymphocytic leukemia (CLL) and other diseases. Cyclin-dependent kinase 
(Cdk) inhibitors, flavopiridol (alvocidib), BMS-387032 (SNS-032), sunitinib and 
sorafenib are currently under evaluation in clinical trials for 
relapsed/refractory CLL. Multi-tyrosine kinase inhibitors including vandetanib 
(ZD6474) bosutinib (SKI-606), TKI258 (CHIR-258), pazopanib (GW786034) and 
axitinib (AG013736) have been also developed for the treatment of lymphoid 
malignancies. Phosphatidylinositol 3-kinases (PI3K ) are a family of lipid 
kinases that mediate signals from cell surface receptors. CAL-101 (GS-1101) is 
an oral PI3Kδ-specific inhibitor which has shown preclinical and clinical 
activity against CLL. This article summarizes recent achievements in the 
mechanism of action, pharmacological properties and clinical activity and 
toxicity of PK and LK inhibitors in CLL.