Heartwood is a physiologically inactive part of the xylem, which is formed as a result of parenchymal cell death and is characterized by the accumulation of extractives that prevent wood from biodegradation. The review summarizes the latest information about the anatomical and biochemical features of heartwood genesis, describes its major stages in the main stand-forming species, and examines the biological role of heartwood. Special attention is given to recent advancements in the study of the genes encoding key enzymes of carbohydrate and phenolic metabolism, hormone metabolism, and some transcription factors that are overexpressed during heartwood formation. The review presents original hypotheses that consider heartwood formation as a form of tissue aging and compare it to programmed cell death.