Brain-region specific gene expression analysis from human alcoholic versus control subjects has allowed unprecedented access to gene co-expression networks that are altered by chronic alcohol consumption. However, the cellular heterogeneity of individual brain regions could compromise interpretations of gene expression data. First and foremost, tissue heterogeneity could restrict or mask detection of significant expression changes occurring within a particular cell type, especially if this population represents a smaller proportion of the total cells in the sample. Second, in silico tools that are currently used in cell-type specific analyses limit interpretations because an observed change in gene expression could be due to the gain or loss of certain cell types, an expression change in all cells or in a subset of cells, or combinations of all of these conditions.