Small heat shock proteins (small HSPs) are molecular chaperones that protect cells against stress by assisting in the correct folding of denatured proteins and thus prevent aggregation of misfolded proteins. Small HSPs also modulate apoptotic pathways by interacting with components of programmed cell death. Furthermore, some small HSPs interact with the cytoskeleton to assist in spatial organization and dynamics of its structural elements. The role of small HSPs has been studied in many disorders, including neurodegenerative disease. Recently, mutations in HSPB1 (HSP27) and HSPB8 (HSP22), two members of the small HSP superfamily, have been associated with inherited peripheral neuropathies. In this review, we will summarize the current knowledge of small HSPs, in particular HSPB1 and HSPB8, and discuss their role in health and disease.