Hairy-cell leukaemia (HCL) was initially described as a distinct clinical entity in 1958. Various types of therapy have been evaluated since this initial description and several are currently important only for historical comparison. Hairy-cell leukaemia serves as an example of rapid progress in the development of effective therapeutic strategies. Splenectomy was the first effective treatment because it resulted in an improvement in cytopenias and relief from symptomatic splenomegaly. However, complete remission of the disease was observed only very rarely. Splenectomy was considered an appropriate initial therapy from the 1950s to the early 1980s, although no randomized controlled studies have ever shown improved survival with this approach. In the early 1980s, more effective treatments were identified, initially interferon-alpha, then the purine analogues 2-deoxycoformycin and 2-chlorodeoxyadenosine (2-CdA). These types of therapy have been so effective that most previous treatments are now obsolete. Although the purine analogues result in sustained remissions in the majority of patients, a relatively small percentage of patients relapse and require other types of therapy. Splenectomy may be necessary in some instances. In this chapter the role of splenectomy is reviewed and other types of therapy of historical interest are presented.