Members of the nuclear-receptor superfamily have well-documented regulatory effects on inflammatory processes. Recent work has highlighted the roles of peroxisome-proliferator-activated receptors (PPARs) and liver X receptors (LXRs) in controlling metabolic and inflammatory programmes of gene expression in macrophages and lymphocytes. Here, we describe recent studies that extend our understanding of how these nuclear receptors, through their interactions with transcription factors and other cell-signalling systems, have important regulatory roles in innate and adaptive immunity. We suggest that by using receptor-specific mechanisms, PPARs and LXRs function in a combinatorial manner with the glucocorticoid receptor to integrate local and systemic responses to inflammation.