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The elusive direct reductive amination between aliphatic amines and aliphatic ketones is reported. This was achieved by using a diphosphine?coordinated iridium catalyst. The applicability and functional?group tolerance were demonstrated by the synthesis of a panel of tertiary amines relevant for medicinal chemistry research. This methodology is promising for implementation in late?stage functionalization and repurposing current retrosynthetic schemes.Direct reductive amination (DRA) is a ubiquitous reaction in organic chemistry. This transformation between a carbonyl group and an amine is most often achieved by using a super stoichiometric amount of hazardous hydride reagents, thus being incompatible with many sensitive functional groups. DRA could also be achieved by means of chemo? or biocatalysis, thereby attracting the interest of industry as well as academic laboratories due to the virtually perfect atom economy. Although DRAs are well?established for substrate pairs such as aldehydes with either 1° or 2° amines as well as ketones with 1° amines, the current methodologies are limited in the case of ketones with 2° amines. Herein, we present a general DRA protocol that overcomes this major limitation by means of iridium catalysis. The applicability of the methodology is demonstrated by accessing an unprecedented range of biologically relevant tertiary amines starting from both aliphatic ketones and aliphatic amines. The choice of a disphosphane ligand (Josiphos A or Xantphos) is essential for the success of the transformation.