A key to the development of nanotechnology will be the ability to make complex nanoscaled three-dimensional structures at low cost and in large numbers. The wide variety of structures in the silicified cell walls of diatoms offers a promising natural source of such materials. Diatom silica can be converted into other materials, with maintenance of detailed morphology. To facilitate the use of diatoms in nanotechnology, specific manipulation of the structure in vivo will be desirable. This article explores the possibilities of manipulating diatom silica structure, by nongenetic and genetic means. Nongenetic influences that affect silica structure include changes in environmental conditions and life cycle stages and the presence or absence of particular compounds. The genetically based natural variation in structure in different diatom species indicates that genetic manipulation is possible. To achieve this, however, several goals must be met. The first is to identify cell wall synthesis (CWS) genes involved in structure formation. The recently completed genome sequence of Thalassiosira pseudonana opens the door for genomic and proteomic approaches to accomplish this. An important method to determine the function of CWS genes will be to modify gene sequences or expression and monitor the effect on structure. Performing gene modifications is straightforward, and modified genes can be introduced into diatoms, but the current inability to replace native diatom genes with modified copies could be a problem. However, there are feasible approaches yet to be applied to achieve this goal. It is very likely that continued development and application of molecular genetic techniques will enable us to specifically modify diatom silicified structures and provide a detailed understanding of the underlying mechanism of their formation.