Over the last decade, cytokine imbalances have been associated with a plethora of diseases. While the Th(1)/Th(2) paradigm is widely used to explain the pathogenesis of immunological diseases, the role of cytokine imbalances for non-immunological diseases is still incompletely defined. The major obstacle here is to assess the extent to which non-immunological diseases are influenced by inflammation. Non-immunological diseases cover the whole spectrum from those triggered by infection-as may be the case for Alzheimer's disease-to those where the immune system has no apparent impact at all. Examples of the latter are bone diseases, including post-menopausal osteoporosis and skeletal malformations. In between there are diseases such as intrinsic asthma and osteoarthritis where the impact of the immune system is unclear. Thus far, imbalances affecting tumour necrosis factor (TNF)-alpha and members of the interleukin (IL)-1 and the TGF superfamily have been found in association with all of these diseases. We speculate here that cytokine imbalance will be found in additional diseases and touch on the role in phylogeny of cytokines outside the immune system.