BTK and ITK are cytoplasmic tyrosine kinases of crucial importance for B and T 
cell development, with loss-of-function mutations causing X-linked 
agammaglobulinemia and susceptibility to severe, frequently lethal, Epstein-Barr 
virus infection, respectively. Over the last few years, considerable efforts 
have been made in order to develop small-molecule inhibitors for these kinases 
to treat lymphocyte malignancies, autoimmunity or allergy/hypersensitivity. The 
rationale is that even if complete lack of BTK or ITK during development causes 
severe immunodeficiency, inactivation after birth may result in a less severe 
phenotype. Moreover, therapy can be transient or only partially block the 
activity of BTK or ITK. Furthermore, a drug-induced B cell deficiency is 
treatable by gamma globulin substitution therapy. The newly developed BTK 
inhibitor PCI-32765, recently renamed Ibrutinib, has already entered several 
clinical trials for various forms of non-Hodgkin lymphoma as well as for 
multiple myeloma. Experimental animal studies have demonstrated highly promising 
treatment effects also in autoimmunity. ITK inhibitors are still under the early 
developmental phase, but it can be expected that such drugs will also become 
very useful. In this study, we present BTK and ITK with their signalling 
pathways and review the development of the corresponding inhibitors.