The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Interferon Regulatory Factor 8 (IRF8), in particular, by targeting natural antisense polynucleotides of Interferon Regulatory Factor 8 (IRF8). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of IRF8.