Primary hyperhidrosis is a pathological disorder of unknown etiology, affecting 0.6-5% of the population, and causing severe functional and social handicaps. As the etiology is unknown, it is not possible to treat the root cause. Recently some differences between affected and non-affected people have been reported. The aim of this review is to summarize these new etiological data. Search of the literature was performed in the PubMed/Medline Database and pertinent articles were retrieved and reviewed. Additional publications were obtained from the references of these articles. Some anatomical and pathophysiological characteristics (as well as enzymatic, metabolic, and neurological dysfunctions) have been observed in hyperhidrotic subjects; three main possible etiological factors predominate. A familial trait seems to exist, and genetic loci associated with hyperhidrosis have been identified. Histological differences were observed in sympathetic ganglia of hyperhidrotic subjects: the ganglia were larger and contained a higher number of ganglion cells. A higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis has been reported. Despite these accumulated data, the etiology of primary hyperhidrosis remains obscure. Nevertheless, three main lines for future research seem to be delineated: genetics, histological observations, and enzymatic studies.