Interest in understanding the isotopic variations of Cu extends to all areas of the Earth and Planetary sciences, including oceanography, cosmochemistry, environmental sciences, as well as beyond into the medical sciences. The need for highly purified Cu fractions from these varied matrix types is critical for the accurate and precise determination of their Cu isotope compositions, and while many different approaches are undertaken to achieve this end, there is also considerable overlap in the chemical purification strategies employed. In this chapter, we outline the steps and processes required to access a natural sample’s Cu isotope composition in an accurate and precise manner—from sample dissolution, through isolation of Cu from the sample matrix and analysis via mass spectrometer. Many of the steps we describe are applicable to the analysis of any isotope system. However, we focus on the methodologies designed for Cu isotope analysis, with any associated specific considerations described in detail.