Increasing evidence indicates that the brain generates signals in a wide-frequency range, including high-frequency brain signals. High-frequency brain signals are also called high-frequency oscillations (HFOs), ripples, or fast ripples. There are no established terms for describing HFOs in a variety of frequency ranges. HFOs are clinically important because early detection of epileptic (or pathologic) high-frequency brain signals may significantly change the clinical management of epilepsy, including pediatric epilepsy. In this article, we review the cerebral mechanisms of HFOs and the maturational changes of HFOs in the developing brain. Newly developed methods for the detection and localization of HFOs are discussed. We describe many recent findings in the literature from invasive electrocorticography recordings, scalp electroencephalography, and magnetoencephalography. We also discuss the clinical importance of HFOs as markers of epileptogenicity and their application in different types of epilepsies. As successful surgical treatment in medically refractory epilepsies largely depends on the identification of epileptogenic zones, the use of HFOs may significantly improve surgical outcomes. Indeed, the removal of brain tissue generating pathological high-frequency signals has been related to better postsurgical outcomes than removal of the seizure onset zones. This indicates that HFOs may mark cortex that needs to be removed to achieve seizure control. The link between the epileptogenic zone and HFOs suggests that their study can elucidate the pathophysiology of epileptogenesis and ictogenesis. In addition, HFOs may reflect the predisposition of the tissue to generate seizures. Finally, we discuss how HFOs can be used to study childhood absence epilepsy, which can only be studied noninvasively.