The cross-coupling reaction of alkyl halides with alkyl metal reagents is a straightforward synthetic method to construct saturated carbon frameworks. Although the development of alkyl–alkyl cross-coupling reactions has lagged behind advances made in the cross-coupling of unsaturated compounds, various catalysts for alkyl–alkyl coupling are now available. The construction of challenging saturated carbon frameworks, such as those incorporating a quaternary carbon or chiral carbon center(s), is accomplished with the appropriate combination of catalyst and coupling partners. This chapter outlines the current understanding and efficient application of alkyl–alkyl cross-coupling reactions. The mechanism of the process is presented for representative catalysts and the scope and limitations of the coupling reaction are discussed for each catalytic system. Successful applications of alkyl–alkyl cross-coupling processes are also described for the stereoselective formation of saturated hydrocarbon frameworks and the synthesis of natural products.