Much of the rising health care costs in aging populations can be attributed to congenital disease and psychiatric and neurologic disorders. Early detection of changes related to these diseases can promote the development of new therapeutic strategies and effective treatments. Changes in tissue, such as damage resulting from continued functional abnormality, often exhibit a time-delay before detection is possible. Methods for detecting functional alterations in endogenous brain fluctuations allow for an early diagnosis before tissue damage occurs, enabling early treatment and a more likely positive outcome. A literature review and comprehensive overview of the current state of knowledge about endogenous brain fluctuations is presented here. Recent findings of the association between various pathological conditions and endogenous fluctuations are discussed. A particular emphasis is placed on research showing the relationship between clinical measures and pathological findings to the dynamics of endogenous fluctuations of the brain. Recent discoveries of methods for detecting abnormal functional connectivity are discussed and future research directions explored. Hum Brain Mapp 2008. © 2008 Wiley-Liss, Inc.