The rhenium–osmium isotopic systematics represents a powerful tool to unravel processes related to the Earth’s formation and evolution, the composition of seawater and the extent of weathering in the past. The increasing usage of the 187Re–187Os chronometer applied to a wide range of Earth’s mantle and crustal materials has been attracting many researchers for decades. Nevertheless, several pitfalls associated with Re–Os methodology have prevented a wider use of this method. This chapter provides a detailed overview of the Re–Os analytical methods that should serve as a basic manual for those who plan to establish this methodology in their lab.