Tumor necrosis factor (TNF) is one of the most important proinflammatory cytokines. It demonstrates a complex pattern of tissue-specific expression and behaves as a product of immediate early transcriptional response in macrophages. These properties have made the regulation of TNF gene, as well as regulation of tightly linked related lymphotoxin a (LTa) and b (LTb) genes, the object of thorough investigation for more than two decades. Some aspects of TNF/LT locus regulation, such as the role of distal TNF-promoter and of NF-kB factors in TNF gene transcription, still remain the object of discussion. Moreover, several recent studies uncovering the molecular mechanisms of immediate early gene activation and that are directly related to TNF gene regulation have not been reflected in published reviews yet. Here, we briefly overview the modern concepts of transcriptional regulation of the TNF/LT locus, with an accent on new data and unanswered questions.