This chapter provides an overview of techniques designed for the creation of Surface-enhanced Raman scattering (SERS) hot spots both in solution and on solid supports. It introduces the self-assembly of spherical and anisotropic nanoparticles in solution, and focuses on a wide variety of techniques to assemble nanoparticles onto solid supports. The chapter describes top-down approaches typically based on lithography techniques. SERS measurements of metal nanoparticles in suspension are usually conducted by adding the analytes to the suspension, which often causes nanoparticle aggregation, thereby creating electromagnetic hot spots. However, controllable aggregation is a critical issue toward providing reproducible SERS signals. For the purpose of biological applications, using biomolecules such as antibodies, proteins, and DNA as linkers also shows great potential due to their high selectivity. One of the earliest examples of nanoparticle aggregation for SERS study of biological molecules was reported by Keating et al.