This critical review shows that diatoms can be a source of inspiration for the synthesis of advanced nanostructured biohybrids. These single cell microalgae are living inside a porous silica shell called 'frustule'. Mimicking this model, silica-based biohybrids have been produced via the so-called sol-gel process. Biomolecules such as proteins, enzymes or antibodies can be trapped within a silica matrix leading to hybrid biosensors and bioreactors. Whole cells remain viable and retain their metabolic activity leading to the formation of living biohybrids that offer new possibilities in the field of biotechnology and nanomedicine. Diatom frustules exhibit an incredible variety of sophisticated shapes; they can be used as 3D hierarchically structured materials for the realization of sensors, photonic devices or microfluidics. They can also be a model for the bio-templated synthesis of nanostructured materials. Diatom nanotechnology is becoming a new field of research where biologists and materials scientists are working together!