Cholesterol oxidation products, i.e. oxysterols, have only recently attracted the attention of biomedical investigators. This sudden increase in interest probably derives from the recent hypotheses on the pathogenesis of chronic human diseases that are closely influenced by associated inflammation, particular that of atherosclerosis and Alzheimer's disease (AD). Indeed, a very efficient way for inflammation to stimulate the further evolution of diseases associated with impaired cholesterol metabolism is by favouring the oxidation of cholesterol via the generation of reactive oxygen species: oxysterols have been consistently demonstrated to be at least one or two orders of magnitude more reactive than unoxidized cholesterol, showing remarkable pro-inflammatory, pro-apoptotic, and pro-fibrogenic effects. It is probable that oxysterols make a significant contribution to the vascular remodelling occurring in atherosclerosis, as they are involved in various key steps of this complex process, such as endothelial cell dysfunction and adhesion of circulating blood cells, foam cell formation and macrophage/SMC interaction. Moreover, changes in brain cholesterol/oxysterols balance with pathological accumulation of cholesterol oxides in the CNS may actually be the missing link between hypercholesterolemia and AD, as has been suggested, not least because an abnormal pattern of cholesterol hydroxylases has been observed in the brain of AD patients but also because amyloid precursor protein and amyloid b have been demonstrated to efficiently oxidize brain cholesterol. The investigation of the molecular signalling behind the aforementioned effects of oxysterols allowed to demonstrate the involvement of defined components of PKC and MAPK enzymatic families, in particular the MEK/ERK pathway, as well as that of redox-sensitive transcription factors like NF-kB and PPARg.