The innate immune defense system involves the activity of endogenous antimicrobial peptides (AMPs), which inhibit the growth of most microbes. In insects, genes encoding AMPs are expressed at basal levels in barrier epithelia and are upregulated systemically in response to infection. To achieve this differentiated immune defense, Drosophila immune gene promoters combine tissue-specific enhancers and signal-dependent response elements. Transcription factors of the Hox, POU and GATA families control tissue-specific expression of AMP genes, either constitutively or in combination with NF-kappaB/Rel family factors that function as 'on-off switches' during infection. Here, we review these different modes of AMP expression and provide a model for transcriptional regulation of AMP genes.