Cyanidioschyzon merolae is a red alga that lives under extreme environmental conditions, such as those found in acidic hot springs. Recently, this alga has been shown to possess various ancestral characteristics including its cellular structure, genomic composition, metabolic pathways and regulatory networks. Initially, C. merolae was established as a model in the field of cell biology, and it was subsequently characterized as one of the model red alga for postgenomic research. To elucidate the functions of genes of interest within this organism, molecular genetics approaches need to be developed in C. merolae. In this paper, we describe the media and protocols required for cultivation of C. merolae, as well as advanced molecular genetic methods that include transient gene expression, antisense gene suppression and target gene disruption.