This article provides an overview of the use of theory and computation to describe the structural, thermodynamic, mechanical, and optical properties of nanoscale materials. Nanoscience provides important opportunities for theory and computation to lead in the discovery process because the experimental tools often provide an incomplete picture of the structure and/or function of nanomaterials, and theory can often fill in missing features crucial to understanding what is being measured. However, there are important challenges to using theory as well, as the systems of interest are usually too large, and the time scales too long, for a purely atomistic level theory to be useful. At the same time, continuum theories that are appropriate for describing larger-scale (micrometer) phenomena are often not accurate for describing the nanoscale. Despite these challenges, there has been important progress in a number of areas, and there are exciting opportunities that we can look forward to as the capabilities of computational facilities continue to expand. Some specific applications that are discussed in this paper include: self-assembly of supramolecular structures, the thermal properties of nanoscale molecular systems (DNA melting and nanoscale water meniscus formation), the mechanical properties of carbon nanotubes and diamond crystals, and the optical properties of silver and gold nanoparticles. molecular dynamics ͉ nanomaterials ͉ nanoparticle ͉ plasmon ͉ self-assembly N anoscience deals with the behavior of matter on length scales where a large number of atoms play a role, but where the system is still small enough that the material does not behave like bulk matter. For example, a 5-nm gold particle, which contains on the order of 10 5 atoms, absorbs light strongly at 520 nm, whereas bulk gold is reflective at this wavelength and small clusters of gold atoms have absorption at shorter wavelengths. The special properties associated with nanoscale systems like this have provided both challenges and opportunities for the use of theory and computation to play a role in the discovery process. The challenges arise from the fact that most theories that describe the properties of matter by using first-principles approaches in which all atoms (and even all electrons in these atoms) are explicitly described are close to or (more often) beyond their capability to describe such systems, even using the largest computer available. At the same time, continuum theories, which play such a useful role for micrometer-scale systems, are sometimes incapable of describing nanoscale properties due to incomplete incorporation of the underlying physics in the size-dependent materials parameters. However, the opportunities for theory to play a role are significant, as nanoscience often provides the smallest systems that are amenable to study using methods that involve macroscopic manipulation of nanoscale structures. Thus, it is possible to measure the structure and thermal properties of a single supramolecular assembly, observe the thermal ...