Ibrutinib (Imbruvica™) is a small molecule, first-in-class, once-daily, orally available, Bruton's tyrosine kinase inhibitor that is under development for the treatment of B cell malignancies, including chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL), as well as multiple myeloma (MM), follicular lymphoma (FL) and Waldenstrom's macroglobulinemia (WM). It has been developed by Pharmacyclics, Inc. and Janssen Biotech, Inc. Ibrutinib acts by blocking B-cell antigen receptor signalling, thereby reducing malignant proliferation of B cells and inducing cell death. Based chiefly on findings from a phase Ib/II study, ibrutinib has been approved in the USA for the treatment of MCL in previously treated patients and is one of the first approvals through the US FDA's Breakthrough Therapy Designation Pathway. An application has been filed in the EU seeking regulatory approval in this indication. In both the USA and EU, further applications have been filed with regulatory bodies seeking approval for the use of ibrutinib in patients with previously treated CLL/small lymphocytic lymphoma (SLL). Phase III trials are underway worldwide to evaluate ibrutinib in the treatment of patients with CLL/SLL, DLBCL and MCL, and the agent is in phase II development for use in WM, FL and MM. This article summarizes the milestones in the development of ibrutinib leading to its first approval in MCL.