The molecular clock provides a valuable means of estimating evolutionary timescales from genetic and biochemical data. Proposed in the early 1960s, it was first applied to amino acid sequences and immunological measures of genetic distances between species. The molecular clock has undergone considerable development over the years, and it retains profound relevance in the genomic era. In this mini-review, we describe the history of the molecular clock, its impact on evolutionary theory, the challenges brought by evidence of evolutionary rate variation among species, and the statistical models that have been developed to account for these heterogeneous rates of genetic change. We explain how the molecular clock can be used to infer rates and timescales of evolution, and we list some of the key findings that have been obtained when molecular clocks have been applied to genomic data. Despite the numerous challenges that it has faced over the decades, the molecular clock continues to offer the most effective method of resolving the details of the evolutionary timescale of the Tree of Life.

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