Objective To review recent advances in understanding the cellular mechanisms that regulate fat distribution. Methods In this review, new insights into depot and sex differences in the developmental origins and growth of adipose tissues as revealed by studies that use new methods, including lineage tracing, are highlighted. Results Variations in fat distribution during normal growth and in response to alterations in nutritional or hormonal status are driven by intrinsic differences in cells found in each adipose depot. Adipose progenitor cells and preadipocytes in different anatomical adipose tissues derive from cell lineages that determine their capacity for proliferation and differentiation. As a result, rates of hypertrophy and hyperplasia during growth and remodeling vary among depots. The metabolic capacities of adipose cells are also determined by variations in the expression of key transcription factors and non-coding RNAs. These developmental events are influenced by sex chromosomes and hormonal and nutrient signals that determine the adipogenic, metabolic, and functional properties of each depot. Conclusions These new developments in the understanding of fat distribution provide a sound basis for understanding the association of body shape and health in men and women with and without obesity.