Purpose of Review A shift in the commitment of human skeletal stem cells (SSCs) from the osteogenic lineage to the adipogenic lineage can result in increased marrow adiposity and bone loss. Advances in understanding the fate decision of SSCs and particularly the intracellular mechanisms controlling bone marrow adipocyte (BMA) differentiation have thus relevance to bone disorders. The aim of this review is to report the recent contributions of Omics studies to the understanding of mechanisms controlling human BMA differentiation. Recent Findings Omics investigations allow the identification of factors involved in BMA differentiation, some of them already known to have relevance for adipogenesis and others not, and highlight the crucial role of epigenetic regulation in the control of SSCs lineage determination. Summary There is a great potential in the use of Omics technologies for a better understanding of BMA differentiation. To draw a more complete picture of this process, efforts must be made in the standardization, compilation and integration of data from different fields. Further expected outcome is the future identification of biomarkers or therapeutic targets in the context of bone disorders.