Small heat shock proteins (sHSPs) associate with nuclei, cytoskeleton and membranes, and as molecular chaperones they bind partially denatured proteins, thereby preventing irreversible protein aggregation during stress. sHSP monomers consist of a conserved alpha-crystallin domain of approximately 90 amino acid residues, bordered by variable amino- and carboxy-terminal extensions. The sHSPs undergo dynamic assembly into mono- and poly-disperse oligomers where the rate of disassembly affects chaperoning. The alpha-crystallin domain contains several beta-strands organized into two beta-sheets responsible for dimer formation, the basic building block of most sHSPS. The amino-terminal extension modulates oligomerization, subunit dynamics and substrate binding, whereas the flexible carboxy-terminal extension promotes solubility, chaperoning and oligomerization, the latter by inter-subunit linkage. Crystallization studies have revealed sHSP structure and function. Additionally, site-directed mutagenesis, biophysical investigations, functional studies and the discovery of relationships between mutated sHSPs and diseases have illuminated the role of sHSP within cells.