In 2004, Thalassiosira pseudonana was the first eukaryotic marine alga to have its genome sequenced. Since then, this species has quickly emerged as a valuable model species for investigating the molecular underpinnings of essentially all aspects of diatom life, particularly bio-morphogenesis of the cell wall. An important prerequisite for the model status of T. pseudonana is the ongoing development of increasingly precise tools to study the function of gene networks and their encoded proteins in vivo. Here, we briefly review the current toolbox for genetic manipulation, highlight specific examples of its application in studying diatom metabolism, and provide a peek into the role of diatoms in the emerging field of silica biotechnology.