Hydrogen production with Chlamydomonas reinhardtii induced by sulphur starvation is a multiphase process while the cell internal metabolism is completely remodelled. The first cellular response is characterized by induction of genes with regulatory functions, followed by a total remodelling of the metabolism to provide reduction equivalents for cellular processes. We were able to characterize all major processes that provide energy and reduction equivalents during hydrogen production. Furthermore, C. reinhardtii showed a strong transcript increase for gene models responsible for stress response and detoxification of oxygen radicals. Finally, we were able to determine potential bottlenecks and target genes for manipulation to increase hydrogen production or to prolong the hydrogen production phase. The investigation of transcriptomic changes during the time course of hydrogen production in C. reinhardtii with microarrays and RNA-seq revealed new insights into the regulation and remodelling of the cell internal metabolism. Both methods showed a good correlation. The microarray platform can be used as a reliable standard tool for routine gene expression analysis. RNA-seq additionally allowed a detailed time-dependent study of gene expression and determination of new genes involved in the hydrogen production process.