The sum of RNA transcripts of a cell, organ structure, or organism can be referred to as transcriptome. An increasing number of studies report on specific and common alterations in the renal transcriptome in human nephropathies. In this review several challenges in transcriptomic analyses of the human kidney are discussed. This includes ways to approach the heterogeneity of the kidney itself as well as the diversity of renal diseases. Conventional and upcoming techniques for transcriptional profiling of minute tissue samples are presented, including so-called next generation sequencing and microRNA detection. Different tools to integrate transcriptomic data in a systematic context are discussed beside the current challenge to combine such results with data sets from other integrative biology technologies.