The intricate patterning of diatom silica frustules at nanometer-to-micrometer scales makes them of interest for a wide range of industrial applications. For some of these applications, a specific size range in nanostructure is required and may be achieved by selecting species with the desired properties. However, as all biological materials, diatom frustules exhibit variability in their morphological parameters and this variability can to some extent be affected and controlled by environmental conditions. In this review, we explore the effects of different environmental factors including salinity, heavy metals, temperature, pH, extracellular Si(OH)(4) or Ge(OH)(4) concentration, light regime, UV irradiance, long-term cultivation, and biotic factors on the nanostructure of diatom frustules. This compilation of studies illustrates that it is possible to affect the nanostructure of diatom frustules in vivo by controlling different environmental factors as well as by direct chemical modification of frustules. We compare these methods and present examples of how these changes affect the range of variability as well as comparing the magnitude of size changes of the most promising methods.