This article reviews the role of the peroxisome in cellular signalling, with particular emphasis on the unique contributions of this organelle to the complex regulatory inter-relationships of cellular processes within the mammalian organism. Among the topics covered are the close alignments between the signalling systems governing peroxisome proliferation and those of the steroid hormone/thyroid hormone/vitamin D nuclear-receptor superfamily; the regulation of the permeability of the peroxisomal membrane; the involvements of lysophosphatidic acid as an intra- and inter-cellular messenger; the special role of the phosphatidylcholine cycle and its derivative messengers in relation to peroxisomal metabolism; peroxisomal contributions to the regulation of oxygen free radical levels in tissues and the significance of these radicals as second messengers; the evidence of peroxisomal influences on inter-cellular signalling from metabolic turnover studies; modifications of the regulatory significance of fatty acids by the peroxisome; the commonalities in metabolic relationships between the peroxisome and other cellular organelles; and regulatory shuttles associated with peroxisomal function. It is concluded that the peroxisome displays several significant interconnections with the cellular-signalling apparatus, that it is capable of imprinting a characteristic influence on the regulatory network in the cell, and that the contributions of this organelle deserve greater consideration in future investigations of cell-signalling phenomena.