Low-frequency fluctuation (LFF) is a phenomenon that has been widely observed in a variety of neurological disorders. LFF has been defined as any periodic variation in brain activity characterized by frequencies lower than 0.1 Hz. Researchers have examined a number of neurological conditions, including Parkinson’s Disease, Alzheimer’s Disease, traumatic brain injury, and attention-deficit/hyperactivity disorder for evidence of LFF. LFF is believed to be related to neuronal synchronization, and its amplitude is correlated with cognitive and motor function in neurological patients. For instance, studies have found differences in the amplitude of LFF between healthy controls and individuals with Parkinson’s Disease. It has also been suggested that alterations in LFF amplitude are linked to cognitive decline in aging, and Parkinson’s Disease has been associated with decreased LFF amplitude in the prefrontal cortex. Additionally, increased LFF amplitude has been linked to higher performance on cognitive tests, suggesting that LFF is important in mediating cognitive performance. Exposure to neurotoxic compounds has also been associated with decreased LFF amplitude and a number of studies have suggested that LFF may be a useful biomarker for neurodegenerative diseases, which could aid in diagnosis and prognosis. Researchers have also proposed that in addition to its diagnostic and prognostic value, LFF amplitude may serve as a potential therapeutic target for these disorders. Currently, there is a need for further research in order to better understand the mechanism underlying the amplitude of LFF, its clinical relevance, and potential applications. Additionally, as LFF can be non-invasively recorded, it represents an inexpensive and relatively easy to administer biomarker. This could be useful not only for diagnostic and prognostic purposes, but also in establishing therapeutic goals with interventions such as pharmacological therapies, exercise, and physical therapy.