Post-translational modifications (PTMs) of histone proteins play a crucial role in the regulation of chromatin structure and functions. Studies in the last few decades have revealed the significance of histone PTMs in key cellular processes including DNA replication, repair, transcription, apoptosis and cell cycle regulation. The PTMs on histones are carried out by chromatin modifiers, which are reversible in nature. The dynamic activity of chromatin modifiers maintains the levels of different PTMs on histones. The modified histones are recognized by reader proteins, which recruit effector proteins to regulate the function. The interplay between histone PTMs and chromatin dynamics plays a major role in the regulation of most of the cellular processes. Importantly, the perturbations in the histone PTMs by various intrinsic or extrinsic factors can cause defects in fundamental cellular processes leading to a wide range of diseases. The proteolytic clipping of histone proteins has also been shown to regulate many biological processes. Histone clipping has been observed from yeast to mammals, suggesting that this mechanism is a conserved epigenetic phenomenon. In this review, we have summarized the significance of histone clipping and provided future directions to comprehend the mechanism of this distinct and poorly understood epigenetic event.