Roots are the primary sites of water stress perception in plants. The aim of this work was to study differential expression of proteins and transcripts in amaranth roots (Amaranthus hypochondriacus L.) when the plants were grown under drought stress. Changes in protein abundance within the roots were examined using two-dimensional electrophoresis and LC/ESI-MS/MS, and the differential expression of transcripts was evaluated with suppression subtractive hybridisation (SSH). Induction of drought stress decreased relative water content in leaves and increased solutes such as proline and total soluble sugars in roots. Differentially expressed proteins such as SOD(Cu-Zn) , heat shock proteins, signalling-related and glycine-rich proteins were identified. Up-regulated transcripts were those related to defence, stress, signalling (Ser, Tyr-kinases and phosphatases) and water transport (aquaporins and nodulins). More noteworthy was identification of the transcription factors DOF1, which has been related to several plant-specific biological processes, and MIF1, whose constitutive expression has been related to root growth reduction and dwarfism. The down-regulated genes/proteins identified were related to cell differentiation (WOX5A) and secondary metabolism (caffeic acid O-methyltransferase, isoflavone reductase-like protein and two different S-adenosylmethionine synthetases). Amaranth root response to drought stress appears to involve a coordinated response of osmolyte accumulation, up-regulation of proteins that control damage from reactive oxygen species, up-regulation of a family of heat shock proteins that stabilise other proteins and up-regulation of transcription factors related to plant growth control.