Leaf senescence, the final phase of leaf development, plays a crucial role in plant fitness and crop improvement, as it enables nutrient remobilization from leaves to reproductive organs like developing seeds. This process involves extensive reprogramming of gene expression, governed by intricate regulatory networks operating across multiple layers of control. The employment of systems approaches using omics-based technologies and the characterization of key regulators has been instrumental in uncovering newly emerging regulatory mechanisms, providing valuable insights into how this orderly degeneration process is fine-tuned. In this review, we present a comprehensive overview of the current research on epigenetic mechanisms as a key layer within regulatory networks, influencing transcription factor activity and modulating the expression of senescence-associated genes. We also discuss recent advances in identifying the role of non-coding RNAs, RNA methylation, and peptide hormones during leaf senescence, which contributes to a deeper understanding of the complex regulatory pathways involved.