Identification of the transcribed regions in the newly sequenced genomes is one of the major challenges of postgenomic biology. Among different alternatives for empirical transcriptome mapping, whole-genome tiling array experiment emerged as the most comprehensive and unbiased approach. This relatively new method uses high-density oligonucleotide arrays with probes chosen uniformly from both strands of the entire genomes including all genic and intergenic regions. By hybridizing the arrays with tissue specific or pooled RNA samples, a genome-wide picture of transcription can be derived. This chapter discusses computational tools and techniques necessary to successfully conduct genome tiling array experiments.